@article{HoffmannOttRaupbachetal.2022,
author = {Hoffmann, Holger and Ott, Christiane and Raupbach, Jana and Andernach, Lars and Renz, Matthias and Grune, Tilman and Hanschen, Franziska S.},
title = {Assessing bioavailability and bioactivity of 4-Hydroxythiazolidine-2-Thiones, newly discovered glucosinolate degradation products formed during domestic boiling of cabbage},
series = {Frontiers in nutrition},
volume = {9},
journal = {Frontiers in nutrition},
publisher = {Frontiers Media},
address = {Lausanne},
issn = {2296-861X},
doi = {10.3389/fnut.2022.941286},
pages = {13},
year = {2022},
abstract = {Glucosinolates are plant secondary metabolites found in cruciferous vegetables (Brassicaceae) that are valued for their potential health benefits. Frequently consumed representatives of these vegetables, for example, are white or red cabbage, which are typically boiled before consumption. Recently, 3-alk(en)yl-4-hydroxythiazolidine-2-thiones were identified as a class of thermal glucosinolate degradation products that are formed during the boiling of cabbage. Since these newly discovered compounds are frequently consumed, this raises questions about their potential uptake and their possible bioactive functions. Therefore, 3-allyl-4-hydroxythiazolidine-2-thione (allyl HTT) and 4-hydroxy-3-(4-(methylsulfinyl) butyl)thiazolidine-2-thione (4-MSOB HTT) as degradation products of the respective glucosinolates sinigrin and glucoraphanin were investigated. After consumption of boiled red cabbage broth, recoveries of consumed amounts of the degradation products in urine collected for 24 h were 18 +/- 5\% for allyl HTT and 21 +/- 4\% for 4-MSOB HTT (mean +/- SD, n = 3). To investigate the stability of the degradation products during uptake and to elucidate the uptake mechanism, both an in vitro stomach and an in vitro intestinal model were applied. The results indicate that the uptake of allyl HTT and 4-MSOB HTT occurs by passive diffusion. Both compounds show no acute cell toxicity, no antioxidant potential, and no change in NAD(P)H dehydrogenase quinone 1 (NQO1) activity up to 100 mu M. However, inhibition of glycogen synthase kinases-3 (GSK-3) in the range of 20\% for allyl HTT for the isoform GSK-3 beta and 29\% for 4-MSOB HTT for the isoform GSK-3 alpha at a concentration of 100 mu M was found. Neither health-promoting nor toxic effects of 3-alk(en)yl-4-hydroxythiazolidine-2-thiones were found in the four tested assays carried out in this study, which contrasts with the properties of other glucosinolate degradation products, such as isothiocyanates.},
language = {en}
}
@article{BishopMachateHenningetal.2022,
author = {Bishop, Christopher Allen and Machate, Tina and Henning, Thorsten and Henkel-Oberl{\"a}nder, Janin and P{\"u}schel, Gerhard and Weber, Daniela and Grune, Tilman and Klaus, Susanne and Weitkunat, Karolin},
title = {Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle},
series = {Nutrition \& Diabetes},
volume = {12},
journal = {Nutrition \& Diabetes},
number = {1},
publisher = {Nature Publishing Group},
address = {London},
issn = {2044-4052},
doi = {10.1038/s41387-022-00200-8},
pages = {9},
year = {2022},
abstract = {Objective: Current data regarding the roles of branched-chain amino acids (BCAA) in metabolic health are rather conflicting, as positive and negative effects have been attributed to their intake. Methods: To address this, individual effects of leucine and valine were elucidated in vivo (C57BL/6JRj mice) with a detailed phenotyping of these supplementations in high-fat (HF) diets and further characterization with in vitro approaches (C2C12 myocytes). Results: Here, we demonstrate that under HF conditions, leucine mediates beneficial effects on adiposity and insulin sensitivity, in part due to increasing energy expenditure-likely contributing partially to the beneficial effects of a higher milk protein intake. On the other hand, valine feeding leads to a worsening of HF-induced health impairments, specifically reducing glucose tolerance/ insulin sensitivity. These negative effects are driven by an accumulation of the valine-derived metabolite 3-hydroxyisobutyrate (3HIB). Higher plasma 3-HIB levels increase basal skeletal muscle glucose uptake which drives glucotoxicity and impairs myocyte insulin signaling. Conclusion: These data demonstrate the detrimental role of valine in an HF context and elucidate additional targetable pathways in the etiology of BCAA-induced obesity and insulin resistance.},
language = {en}
}
@misc{WeberKochlikDemuthetal.2020,
author = {Weber, Daniela and Kochlik, Bastian and Demuth, Ilja and Steinhagen-Thiessen, Elisabeth and Grune, Tilman and Norman, Kristina},
title = {Plasma carotenoids, tocopherols and retinol},
series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
issn = {1866-8372},
doi = {10.25932/publishup-51599},
url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-515996},
pages = {10},
year = {2020},
abstract = {Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micro-nutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, alpha-carotene, alpha-tocopherol, beta-cryptoxanthin (only in women), and gamma-tocopherol (only in men). beta-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, alpha-carotene (both inverse), alpha-tocopherol, gamma-tocopherol, and beta-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for beta-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and alpha-carotene concentration in older subjects, bioavailability studies in older participants are necessary.},
language = {en}
}
@misc{KesslerHornemannRudovichetal.2020,
author = {Kessler, Katharina and Hornemann, Silke and Rudovich, Natalia and Weber, Daniela and Grune, Tilman and Kramer, Achim and Pfeiffer, Andreas F. H. and Pivovarova-Ramich, Olga},
title = {Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers},
series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
number = {2},
issn = {1866-8372},
doi = {10.25932/publishup-51207},
url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-512079},
pages = {14},
year = {2020},
abstract = {Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies.},
language = {en}
}
@misc{RaupbachOttKoenigetal.2020,
author = {Raupbach, Jana and Ott, Christiane and K{\"o}nig, Jeannette and Grune, Tilman},
title = {Proteasomal degradation of glycated proteins depends on substrate unfolding},
series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
issn = {1866-8372},
doi = {10.25932/publishup-52757},
url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-527570},
pages = {516 -- 524},
year = {2020},
abstract = {The Maillard reaction generates protein modifications which can accumulate during hyperglycemia or aging and may have inflammatory consequences. The proteasome is one of the major intracellular systems involved in the proteolytic degradation of modified proteins but its role in the degradation of glycated proteins is scarcely studied. In this study, chemical and structural changes of glycated myoglobin were analyzed and its degradation by 20S proteasome was studied. Myoglobin was incubated with physiological (5-10 mM), moderate (50-100 mM) and severe levels (300 mM) of glucose or methylglyoxal (MGO, 50 mM). Glycation increased myoglobin's fluorescence and surface hydrophobicity. Severe glycation generated crosslinked proteins as shown by gel electrophoresis. The concentration of advanced glycation endproducts (AGEs) N-epsilon-carboxymethyl lysine (CML), N-epsilon-carboxyethyl lysine (CEL), methylglyoxal-derived hydroimidazolone-1 (MG-H1), pentosidine and pyrraline was analyzed after enzymatic hydrolysis followed by UPLC-MS/MS. Higher concentrations of glucose increased all analyzed AGEs and incubation with MGO led to a pronounced increase of CEL and MG-H1. The binding of the heme group to apo-myoglobin was decreased with increasing glycation indicating the loss of tertiary protein structure. Proteasomal degradation of modified myoglobin compared to native myoglobin depends on the degree of glycation: physiological conditions decreased proteasomal degradation whereas moderate glycation increased degradation. Severe glycation again decreased proteolytic cleavage which might be due to crosslinking of protein monomers. The activity of the proteasomal subunit beta 5 is influenced by the presence of glycated myoglobin. In conclusion, the role of the proteasome in the degradation of glycated proteins is highly dependent on the level of glycation and consequent protein unfolding.},
language = {en}
}
@article{WiedmerJungCastroetal.2020,
author = {Wiedmer, Petra and Jung, Tobias and Castro, Jose Pedro and Pomatto, Laura C. D. and Sun, Patrick Y. and Davies, Kelvin J. A. and Grune, Tilman},
title = {Sarcopenia},
series = {Ageing research reviews : ARR},
volume = {65},
journal = {Ageing research reviews : ARR},
publisher = {Elsevier},
address = {Clare},
issn = {1568-1637},
doi = {10.1016/j.arr.2020.101200},
pages = {17},
year = {2020},
abstract = {Sarcopenia represents a muscle-wasting syndrome characterized by progressive and generalized degenerative loss of skeletal muscle mass, quality, and strength occurring during normal aging. Sarcopenia patients are mainly suffering from the loss in muscle strength and are faced with mobility disorders reducing their quality of life and are, therefore, at higher risk for morbidity (falls, bone fracture, metabolic diseases) and mortality.
Several molecular mechanisms have been described as causes for sarcopenia that refer to very different levels of muscle physiology. These mechanisms cover e. g. function of hormones (e. g. IGF-1 and Insulin), muscle fiber composition and neuromuscular drive, myo-satellite cell potential to differentiate and proliferate, inflammatory pathways as well as intracellular mechanisms in the processes of proteostasis and mitochondrial function.
In this review, we describe sarcopenia as a muscle-wasting syndrome distinct from other atrophic diseases and summarize the current view on molecular causes of sarcopenia development as well as open questions provoking further research efforts for establishing efficient lifestyle and therapeutic interventions.},
language = {en}
}
@article{Grune2020,
author = {Grune, Tilman},
title = {Oxidized protein aggregates},
series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
volume = {150},
journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
publisher = {Elsevier},
address = {New York},
issn = {0891-5849},
doi = {10.1016/j.freeradbiomed.2020.02.014},
pages = {120 -- 124},
year = {2020},
abstract = {The study of protein aggregates has a long history. While in the first decades until the 80ies of the 20th century only the observation of the presence of such aggregates was reported, later the biochemistry of the formation and the biological effects of theses aggregates were described. This review focusses on the complexity of the biological effects of protein aggregates and its potential role in the aging process.},
language = {en}
}
@article{KehmJaehnertDeubeletal.2020,
author = {Kehm, Richard and J{\"a}hnert, Markus and Deubel, Stefanie and Flore, Tanina and K{\"o}nig, Jeannette and Jung, Tobias and Stadion, Mandy and Jonas, Wenke and Sch{\"u}rmann, Annette and Grune, Tilman and H{\"o}hn, Annika},
title = {Redox homeostasis and cell cycle activation mediate beta-cell mass expansion in aged, diabetes-prone mice under metabolic stress conditions: role of thioredoxin-interacting protein (TXNIP)},
series = {Redox Biology},
volume = {37},
journal = {Redox Biology},
publisher = {Elsevier},
address = {Amsterdam},
issn = {2213-2317},
doi = {10.1016/j.redox.2020.101748},
pages = {11},
year = {2020},
abstract = {Overnutrition contributes to insulin resistance, obesity and metabolic stress, initiating a loss of functional beta-cells and diabetes development. Whether these damaging effects are amplified in advanced age is barely investigated. Therefore, New Zealand Obese (NZO) mice, a well-established model for the investigation of human obesity-associated type 2 diabetes, were fed a metabolically challenging diet with a high-fat, carbohydrate restricted period followed by a carbohydrate intervention in young as well as advanced age. Interestingly, while young NZO mice developed massive hyperglycemia in response to carbohydrate feeding, leading to beta-cell dysfunction and cell death, aged counterparts compensated the increased insulin demand by persistent beta-cell function and beta-cell mass expansion. Beta-cell loss in young NZO islets was linked to increased expression of thioredoxin-interacting protein (TXNIP), presumably initiating an apoptosis-signaling cascade via caspase-3 activation. In contrast, islets of aged NZOs exhibited a sustained redox balance without changes in TXNIP expression, associated with higher proliferative potential by cell cycle activation. These findings support the relevance of a maintained proliferative potential and redox homeostasis for preserving islet functionality under metabolic stress, with the peculiarity that this adaptive response emerged with advanced age in diabetesprone NZO mice.},
language = {en}
}
@article{HaeseliDeubelJungetal.2020,
author = {H{\"a}seli, Steffen and Deubel, Stefanie and Jung, Tobias and Grune, Tilman and Ott, Christiane},
title = {Cardiomyocyte contractility and autophagy in a premature senescence model of cardiac aging},
series = {Oxidative medicine and cellular longevity},
volume = {2020},
journal = {Oxidative medicine and cellular longevity},
number = {Special Issue},
publisher = {Landes Bioscience},
address = {Austin, Tex.},
issn = {1942-0994},
doi = {10.1155/2020/8141307},
pages = {14},
year = {2020},
abstract = {Globally, cardiovascular diseases are the leading cause of death in the aging population. While the clinical pathology of the aging heart is thoroughly characterized, underlying molecular mechanisms are still insufficiently clarified. The aim of the present study was to establish an in vitro model system of cardiomyocyte premature senescence, culturing heart muscle cells derived from neonatal C57Bl/6J mice for 21 days. Premature senescence of neonatal cardiac myocytes was induced by prolonged culture time in an oxygen-rich postnatal environment. Age-related changes in cellular function were determined by senescence-associated beta-galactosidase activity, increasing presence of cell cycle regulators, such as p16, p53, and p21, accumulation of protein aggregates, and restricted proteolysis in terms of decreasing (macro-)autophagy. Furthermore, the culture system was functionally characterized for alterations in cell morphology and contractility. An increase in cellular size associated with induced expression of atrial natriuretic peptides demonstrated a stress-induced hypertrophic phenotype in neonatal cardiomyocytes. Using the recently developed analytical software tool Myocyter, we were able to show a spatiotemporal constraint in spontaneous contraction behavior during cultivation. Within the present study, the 21-day culture of neonatal cardiomyocytes was defined as a functional model system of premature cardiac senescence to study age-related changes in cardiomyocyte contractility and autophagy.},
language = {en}
}
@article{RaupbachOttKoenigetal.2020,
author = {Raupbach, Jana and Ott, Christiane and K{\"o}nig, Jeannette and Grune, Tilman},
title = {Proteasomal degradation of glycated proteins depends on substrate unfolding: Preferred degradation of moderately modified myoglobin},
series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
volume = {152},
journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
publisher = {Elsevier},
address = {New York},
issn = {0891-5849},
doi = {10.1016/j.freeradbiomed.2019.11.024},
pages = {516 -- 524},
year = {2020},
abstract = {The Maillard reaction generates protein modifications which can accumulate during hyperglycemia or aging and may have inflammatory consequences. The proteasome is one of the major intracellular systems involved in the proteolytic degradation of modified proteins but its role in the degradation of glycated proteins is scarcely studied. In this study, chemical and structural changes of glycated myoglobin were analyzed and its degradation by 20S proteasome was studied. Myoglobin was incubated with physiological (5-10 mM), moderate (50-100 mM) and severe levels (300 mM) of glucose or methylglyoxal (MGO, 50 mM). Glycation increased myoglobin's fluorescence and surface hydrophobicity. Severe glycation generated crosslinked proteins as shown by gel electrophoresis. The concentration of advanced glycation endproducts (AGEs) N-epsilon-carboxymethyl lysine (CML), N-epsilon-carboxyethyl lysine (CEL), methylglyoxal-derived hydroimidazolone-1 (MG-H1), pentosidine and pyrraline was analyzed after enzymatic hydrolysis followed by UPLC-MS/MS. Higher concentrations of glucose increased all analyzed AGEs and incubation with MGO led to a pronounced increase of CEL and MG-H1. The binding of the heme group to apo-myoglobin was decreased with increasing glycation indicating the loss of tertiary protein structure. Proteasomal degradation of modified myoglobin compared to native myoglobin depends on the degree of glycation: physiological conditions decreased proteasomal degradation whereas moderate glycation increased degradation. Severe glycation again decreased proteolytic cleavage which might be due to crosslinking of protein monomers. The activity of the proteasomal subunit beta 5 is influenced by the presence of glycated myoglobin. In conclusion, the role of the proteasome in the degradation of glycated proteins is highly dependent on the level of glycation and consequent protein unfolding.},
language = {en}
}
@article{KesslerHornemannRudovichetal.2020,
author = {Kessler, Katharina and Hornemann, Silke and Rudovich, Natalia and Weber, Daniela and Grune, Tilman and Kramer, Achim and Pfeiffer, Andreas F. H. and Pivovarova-Ramich, Olga},
title = {Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers},
series = {Nutrients},
journal = {Nutrients},
number = {2},
publisher = {MDPI},
address = {Basel},
issn = {2072-6643},
doi = {10.3390/nu12020340},
pages = {1 -- 12},
year = {2020},
abstract = {Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies.},
language = {en}
}
@article{WeberKochlikDemuthetal.2020,
author = {Weber, Daniela and Kochlik, Bastian and Demuth, Ilja and Steinhagen-Thiessen, Elisabeth and Grune, Tilman and Norman, Kristina},
title = {Plasma carotenoids, tocopherols and retinol},
series = {Redox Biology},
volume = {32},
journal = {Redox Biology},
publisher = {Elsevier},
address = {Amsterdam},
issn = {2213-2317},
doi = {10.1016/j.redox.2020.101461},
pages = {1 -- 8},
year = {2020},
abstract = {Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micro-nutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, alpha-carotene, alpha-tocopherol, beta-cryptoxanthin (only in women), and gamma-tocopherol (only in men). beta-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, alpha-carotene (both inverse), alpha-tocopherol, gamma-tocopherol, and beta-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for beta-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and alpha-carotene concentration in older subjects, bioavailability studies in older participants are necessary.},
language = {en}
}
@misc{KoenigGruneOtt2019,
author = {K{\"o}nig, Jeannette and Grune, Tilman and Ott, Christiane},
title = {Assessing autophagy in murine skeletal muscle: current findings to modulate and quantify the autophagic flux},
series = {Current opinion in clinical nutrition and metabolic care},
volume = {22},
journal = {Current opinion in clinical nutrition and metabolic care},
number = {5},
publisher = {Lippincott Williams \& Wilkins},
address = {Philadelphia},
issn = {1363-1950},
doi = {10.1097/MCO.0000000000000579},
pages = {355 -- 362},
year = {2019},
abstract = {Purpose of review In addition to the currently available lysosomotropic drugs and autophagy whole-body knockout mouse models, we provide alternative methods that enable the modulation and detection of autophagic flux in vivo, discussing advantages and disadvantages of each method. Recent findings With the autophagosome-lysosome fusion inhibitor colchicine in skeletal muscle and temporal downregulation of autophagy using a novel Autophagy related 5-short hairpin RNA (Atg5-shRNA) mouse model we mention two models that directly modulate autophagy flux in vivo. Furthermore, methods to quantify autophagy flux, such as mitophagy transgenic reporters, in situ immunofluorescent staining and multispectral imaging flow cytometry, in mature skeletal muscle and cells are addressed. To achieve clinical benefit, less toxic, temporary and cell-type-specific modulation of autophagy should be pursued further. A temporary knockdown as described for the Atg5-shRNA mice could provide a first insight into possible implications of autophagy inhibition. However, it is also important to take a closer look into the methods to evaluate autophagy after harvesting the tissue. In particular caution is required when experimental conditions can influence the final measurement and this should be pretested carefully.},
language = {en}
}
@article{CastanoMartinezSchumacherSchumacheretal.2019,
author = {Casta{\~n}o Mart{\´i}nez, Mar{\´i}a Teresa and Schumacher, Fabian and Schumacher, Silke and Kochlik, Bastian and Weber, Daniela and Grune, Tilman and Biemann, Ronald and McCann, Adrian and Abraham, Klaus and Weikert, Cornelia and Kleuse, Burkhard and Sch{\"u}rmann, Annette and Laeger, Thomas},
title = {Methionine restriction prevents onset of type 2 diabetes in NZO mice},
series = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology},
volume = {33},
journal = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology},
number = {6},
publisher = {Federation of American Societies for Experimental Biology},
address = {Bethesda},
issn = {0892-6638},
doi = {10.1096/fj.201900150R},
pages = {7092 -- 7102},
year = {2019},
abstract = {Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans. New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes, were placed on isocaloric high-fat diets (protein, 16 kcal\%; carbohydrate, 52 kcal\%; fat, 32 kcal\%) that provided methionine at control (Con; 0.86\% methionine) or low levels (0.17\%) for 9 wk. Markers of glucose homeostasis and insulin sensitivity were analyzed. Among humans, low methionine intake and circulating FGF21 levels were investigated by comparing a vegan and a vegetarian diet to an omnivore diet and evaluating the effect of a short-term vegetarian diet on FGF21 induction. In comparison with the Con group, MR led to elevated plasma FGF21 levels and prevented the onset of hyperglycemia in NZO mice. MR-fed mice exhibited increased insulin sensitivity, higher plasma adiponectin levels, increased EE, and up-regulated expression of thermogenic genes in subcutaneous white adipose tissue. Food intake and fat mass did not change. Plasma FGF21 levels were markedly higher in vegan humans compared with omnivores, and circulating FGF21 levels increased significantly in omnivores after 4 d on a vegetarian diet. These data suggest that MR induces FGF21 and protects NZO mice from high-fat diet-induced glucose intolerance and type 2 diabetes. The normoglycemic phenotype in vegans and vegetarians may be caused by induced FGF21. MR akin to vegan and vegetarian diets in humans may offer metabolic benefits via increased circulating levels of FGF21 and merits further investigation.-Castano-Martinez, T., Schumacher, F., Schumacher, S., Kochlik, B., Weber, D., Grune, T., Biemann, R., McCann, A., Abraham, K., Weikert, C., Kleuser, B., Schurmann, A., Laeger, T. Methionine restriction prevents onset of type 2 diabetes in NZO mice.},
language = {en}
}
@article{SchroeterNeugartSchreineretal.2019,
author = {Schr{\"o}ter, David and Neugart, Susanne and Schreiner, Monika and Grune, Tilman and Rohn, Sascha and Ott, Christiane},
title = {Amaranth's 2-Caffeoylisocitric Acid—An Anti-Inflammatory Caffeic Acid Derivative That Impairs NF-κB Signaling in LPS-Challenged RAW 264.7 Macrophages},
series = {Nutrients},
volume = {11},
journal = {Nutrients},
number = {3},
publisher = {MDPI},
address = {Basel},
issn = {2072-6643},
doi = {10.3390/nu11030571},
pages = {14},
year = {2019},
abstract = {For centuries, Amaranthus sp. were used as food, ornamentals, and medication. Molecular mechanisms, explaining the health beneficial properties of amaranth, are not yet understood, but have been attributed to secondary metabolites, such as phenolic compounds. One of the most abundant phenolic compounds in amaranth leaves is 2-caffeoylisocitric acid (C-IA) and regarding food occurrence, C-IA is exclusively found in various amaranth species. In the present study, the anti-inflammatory activity of C-IA, chlorogenic acid, and caffeic acid in LPS-challenged macrophages (RAW 264.7) has been investigated and cellular contents of the caffeic acid derivatives (CADs) were quantified in the cells and media. The CADs were quantified in the cell lysates in nanomolar concentrations, indicating a cellular uptake. Treatment of LPS-challenged RAW 264.7 cells with 10 µM of CADs counteracted the LPS effects and led to significantly lower mRNA and protein levels of inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin 6, by directly decreasing the translocation of the nuclear factor κB/Rel-like containing protein 65 into the nucleus. This work provides new insights into the molecular mechanisms that attribute to amaranth's anti-inflammatory properties and highlights C-IA's potential as a health-beneficial compound for future research.},
language = {en}
}
@article{KehmRueckriemenWeberetal.2019,
author = {Kehm, Richard and R{\"u}ckriemen, Jana and Weber, Daniela and Deubel, Stefanie and Grune, Tilman and H{\"o}hn, Annika},
title = {Endogenous advanced glycation end products in pancreatic islets after short-term carbohydrate intervention in obese, diabetes-prone mice},
series = {Nutrition \& Diabetes},
volume = {9},
journal = {Nutrition \& Diabetes},
publisher = {Nature Publ. Group},
address = {London},
issn = {2044-4052},
doi = {10.1038/s41387-019-0077-x},
pages = {5},
year = {2019},
abstract = {Diet-induced hyperglycemia is described as one major contributor to the formation of advanced glycation end products (AGEs) under inflammatory conditions, crucial in type 2 diabetes progression. Previous studies have indicated high postprandial plasma AGE-levels in diabetic patients and after long-term carbohydrate feeding in animal models. Pancreatic islets play a key role in glucose metabolism; thus, their susceptibility to glycation reactions due to high amounts of dietary carbohydrates is of special interest. Therefore, diabetes-prone New Zealand Obese (NZO) mice received either a carbohydrate-free, high-fat diet (CFD) for 11 weeks or were additionally fed with a carbohydrate-rich diet (CRD) for 7 days. In the CRD group, hyperglycemia and hyperinsulinemia were induced accompanied by increasing plasma 3-nitrotyrosine (3-NT) levels, higher amounts of 3-NT and inducible nitric oxide synthase (iNOS) within pancreatic islets. Furthermore, N-epsilon-carboxymethyllysine (CML) was increased in the plasma of CRD-fed NZO mice and substantially higher amounts of arg-pyrimidine, pentosidine and the receptor for advanced glycation end products (RAGE) were observed in pancreatic islets. These findings indicate that a short-term intervention with carbohydrates is sufficient to form endogenous AGEs in plasma and pancreatic islets of NZO mice under hyperglycemic and inflammatory conditions.},
language = {en}
}
@article{CastroFernandoReegetal.2019,
author = {Castro, Jose Pedro and Fernando, Raquel and Reeg, Sandra and Meinl, Walter and Almeida, Henrique and Grune, Tilman},
title = {Non-enzymatic cleavage of Hsp90 by oxidative stress leads to actin aggregate formation},
series = {Redox Biology},
volume = {21},
journal = {Redox Biology},
publisher = {Elsevier},
address = {Amsterdam},
issn = {2213-2317},
doi = {10.1016/j.redox.2019.101108},
pages = {10},
year = {2019},
abstract = {Aging is accompanied by the accumulation of oxidized proteins. To remove them, cells employ the proteasomal and autophagy-lysosomal systems; however, if the clearance rate is inferior to its formation, protein aggregates form as a hallmark of proteostasis loss. In cells, during stress conditions, actin aggregates accumulate leading to impaired proliferation and reduced proteasomal activity, as observed in cellular senescence. The heat shock protein 90 (Hsp90) is a molecular chaperone that binds and protects the proteasome from oxidative inactivation. We hypothesized that in oxidative stress conditions a malfunction of Hsp90 occurs resulting in the aforementioned protein aggregates. Here, we demonstrate that upon oxidative stress Hsp90 loses its function in a highly specific non-enzymatic iron-catalyzed oxidation event and its breakdown product, a cleaved form of Hsp90 (Hsp90cl), acquires a new function in mediating the accumulation of actin aggregates. Moreover, the prevention of Hsp90 cleavage reduces oxidized actin accumulation, whereas transfection of the cleaved form of Hsp90 leads to an enhanced accumulation of oxidized actin. This indicates a clear role of the Hsp90cl in the aggregation of oxidized proteins.},
language = {en}
}
@article{KoelmanPivovarovaRamichPfeifferetal.2019,
author = {Koelman, Liselot A. and Pivovarova-Ramich, Olga and Pfeiffer, Andreas F. H. and Grune, Tilman and Aleksandrova, Krasimira},
title = {Cytokines for evaluation of chronic inflammatory status in ageing research},
series = {Immunity \& Ageing},
volume = {16},
journal = {Immunity \& Ageing},
publisher = {BMC},
address = {London},
issn = {1742-4933},
doi = {10.1186/s12979-019-0151-1},
pages = {12},
year = {2019},
abstract = {Background: There is a growing interest in the role of inflammageing for chronic disease development. Cytokines are potent soluble immune mediators that can be used as target biomarkers of inflammageing; however, their measurement in human samples has been challenging. This study aimed to assess the reliability of a pro- and anti-inflammatory cytokine panel in a sample of healthy people measured with a novel electrochemiluminescent multiplex immunoassay platform (Meso Scale Discovery, MSD), and to characterize their associations with metabolic and inflammatory phenotypes.},
language = {en}
}
@misc{CastroWardelmannGruneetal.2018,
author = {Castro, Jos{\´e} Pedro and Wardelmann, Kristina and Grune, Tilman and Kleinridders, Andr{\´e}},
title = {Mitochondrial chaperones in the brain},
series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
number = {1031},
issn = {1866-8372},
doi = {10.25932/publishup-46065},
url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-460650},
pages = {15},
year = {2018},
abstract = {The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA) mutations, reactive oxygen species, and misfolded and aggregated proteins. Thus, mitochondria need to employ specific mechanisms to avoid or ameliorate the rise of damaged proteins that contribute to aberrant mitochondrial function and oxidative stress. To maintain mitochondria homeostasis (mitostasis), cells evolved molecular chaperones that shuttle, refold, or in coordination with proteolytic systems, help to maintain a low steady-state level of misfolded/aggregated proteins. Their importance is exemplified by the occurrence of various brain diseases which exhibit reduced action of chaperones. Chaperone loss (expression and/or function) has been observed during aging, metabolic diseases such as type 2 diabetes and in neurode-generative diseases such as Alzheimer's (AD), Parkinson's (PD) or even Huntington's (HD) diseases, where the accumulation of damage proteins is evidenced. Within this perspective, we propose that proper brain function is maintained by the joint action of mitochondrial chaperones to ensure and maintain mitostasis contributing to brain health, and that upon failure, alter brain function which can cause metabolic diseases.},
language = {en}
}
@article{FernandoDrescherNowotnyetal.2018,
author = {Fernando, Raquel and Drescher, Cathleen and Nowotny, Kerstin and Grune, Tilman and Castro, Jose Pedro},
title = {Impaired proteostasis during skeletal muscle aging},
series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
volume = {132},
journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
publisher = {Elsevier},
address = {New York},
issn = {0891-5849},
doi = {10.1016/j.freeradbiomed.2018.08.037},
pages = {58 -- 66},
year = {2018},
abstract = {Aging is a complex phenomenon that has detrimental effects on tissue homeostasis. The skeletal muscle is one of the earliest tissues to be affected and to manifest age-related changes such as functional impairment and the loss of mass. Common to these alterations and to most of tissues during aging is the disruption of the proteostasis network by detrimental changes in the ubiquitin-proteasomal system (UPS) and the autophagy-lysosomal system (ALS). In fact, during aging the accumulation of protein aggregates, a process mainly driven by increased levels of oxidative stress, has been observed, clearly demonstrating UPS and ALS dysregulation. Since the UPS and ALS are the two most important pathways for the removal of misfolded and aggregated proteins and also of damaged organelles, we provide here an overview on the current knowledge regarding the connection between the loss of proteostasis and skeletal muscle functional impairment and also how redox regulation can play a role during aging. Therefore, this review serves for a better understanding of skeletal muscle aging in regard to the loss of proteostasis and how redox regulation can impact its function and maintenance.},
language = {en}
}
@article{JohnGruneOttetal.2018,
author = {John, Cathleen and Grune, Jana and Ott, Christiane and Nowotny, Kerstin and Deubel, Stefanie and K{\"u}hne, Arne and Schubert, Carola and Kintscher, Ulrich and Regitz-Zagrosek, Vera and Grune, Tilman},
title = {Sex Differences in Cardiac Mitochondria in the New Zealand Obese Mouse},
series = {Frontiers in Endocrinology},
volume = {9},
journal = {Frontiers in Endocrinology},
publisher = {Frontiers Research Foundation},
address = {Lausanne},
issn = {1664-2392},
doi = {10.3389/fendo.2018.00732},
pages = {9},
year = {2018},
abstract = {Background: Obesity is a risk factor for diseases including type 2 diabetes mellitus (T2DM) and cardiovascular disorders. Diabetes itself contributes to cardiac damage. Thus, studying cardiovascular events and establishing therapeutic intervention in the period of type T2DM onset and manifestation are of highest importance. Mitochondrial dysfunction is one of the pathophysiological mechanisms leading to impaired cardiac function. Methods: An adequate animal model for studying pathophysiology of T2DM is the New Zealand Obese (NZO) mouse. These mice were maintained on a high-fat diet (HFD) without carbohydrates for 13 weeks followed by 4 week HFD with carbohydrates. NZO mice developed severe obesity and only male mice developed manifest T2DM. We determined cardiac phenotypes and mitochondrial function as well as cardiomyocyte signaling in this model. Results: The development of an obese phenotype and T2DM in male mice was accompanied by an impaired systolic function as judged by echocardiography and MyH6/7 expression. Moreover, the mitochondrial function only in male NZO hearts was significantly reduced and ERK1/2 and AMPK protein levels were altered. Conclusions: This is the first report demonstrating that the cardiac phenotype in male diabetic NZO mice is associated with impaired cardiac energy function and signaling events.},
language = {en}
}
@article{FernandoDrescherDeubeletal.2018,
author = {Fernando, Raquel and Drescher, Cathleen and Deubel, Stefanie and Jung, Tobias and Ost, Mario and Klaus, Susanne and Grune, Tilman and Castro, Jose Pedro},
title = {Low proteasomal activity in fast skeletal muscle fibers is not associated with increased age-related oxidative damage},
series = {Experimental gerontology},
volume = {117},
journal = {Experimental gerontology},
publisher = {Elsevier},
address = {Oxford},
issn = {0531-5565},
doi = {10.1016/j.exger.2018.10.018},
pages = {45 -- 52},
year = {2018},
abstract = {The skeletal muscle is a crucial tissue for maintaining whole body homeostasis. Aging seems to have a disruptive effect on skeletal muscle homeostasis including proteostasis. However, how aging specifically impacts slow and fast twitch fiber types remains elusive. Muscle proteostasis is largely maintained by the proteasomal system. Here we characterized the proteasomal system in two different fiber types, using a non-sarcopenic aging model. By analyzing the proteasomal activity and amount, as well as the polyubiquitinated proteins and the level of protein oxidation in Musculus soleus (Sol) and Musculus extensor digitorum longus (EDL), we found that the slow twitch Sol muscle shows an overall higher respiratory and proteasomal activity in young and old animals. However, especially during aging the fast twitch EDL muscle reduces protein oxidation by an increase of antioxidant capacity. Thus, under adaptive non-sarcopenic conditions, the two fibers types seem to have different strategies to avoid age-related changes.},
language = {en}
}
@article{CastroWardelmannGruneetal.2018,
author = {Castro, Jose Pedro and Wardelmann, Kristina and Grune, Tilman and Kleinridders, Andre},
title = {Mitochondrial Chaperones in the Brain},
series = {Frontiers in Endocrinology},
volume = {9},
journal = {Frontiers in Endocrinology},
publisher = {Frontiers Research Foundation},
address = {Lausanne},
issn = {1664-2392},
doi = {10.3389/fendo.2018.00196},
pages = {13},
year = {2018},
abstract = {The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA) mutations, reactive oxygen species, and misfolded and aggregated proteins. Thus, mitochondria need to employ specific mechanisms to avoid or ameliorate the rise of damaged proteins that contribute to aberrant mitochondrial function and oxidative stress. To maintain mitochondria homeostasis (mitostasis), cells evolved molecular chaperones that shuttle, refold, or in coordination with proteolytic systems, help to maintain a low steady-state level of misfolded/aggregated proteins. Their importance is exemplified by the occurrence of various brain diseases which exhibit reduced action of chaperones. Chaperone loss (expression and/or function) has been observed during aging, metabolic diseases such as type 2 diabetes and in neurode-generative diseases such as Alzheimer's (AD), Parkinson's (PD) or even Huntington's (HD) diseases, where the accumulation of damage proteins is evidenced. Within this perspective, we propose that proper brain function is maintained by the joint action of mitochondrial chaperones to ensure and maintain mitostasis contributing to brain health, and that upon failure, alter brain function which can cause metabolic diseases.},
language = {en}
}
@article{NowotnyCastroHugoetal.2018,
author = {Nowotny, Kerstin and Castro, Jose Pedro and Hugo, Martin and Braune, Sabine and Weber, Daniela and Pignitter, Marc and Somoza, Veronika and Bornhorst, Julia and Schwerdtle, Tanja and Grune, Tilman},
title = {Oxidants produced by methylglyoxal-modified collagen trigger ER stress and apoptosis in skin fibroblasts},
series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
volume = {120},
journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
publisher = {Elsevier},
address = {New York},
issn = {0891-5849},
doi = {10.1016/j.freeradbiomed.2018.03.022},
pages = {102 -- 113},
year = {2018},
abstract = {Methylglyoxal (MG), a highly reactive dicarbonyl, interacts with proteins to form advanced glycation end products (AGEs). AGEs include a variety of compounds which were shown to have damaging potential and to accumulate in the course of different conditions such as diabetes mellitus and aging. After confirming collagen as a main target for MG modifications in vivo within the extracellular matrix, we show here that MG-collagen disrupts fibroblast redox homeostasis and induces endoplasmic reticulum (ER) stress and apoptosis. In particular, MG-collagen-induced apoptosis is associated with the activation of the PERK-eIF2 alpha pathway and caspase-12. MG-collagen contributes to altered redox homeostasis by directly generating hydrogen peroxide and oxygen-derived free radicals. The induction of ER stress in human fibroblasts was confirmed using collagen extracts isolated from old mice in which MG-derived AGEs were enriched. In conclusion, MG-derived AGEs represent one factor contributing to diminished fibroblast function during aging.},
language = {en}
}
@misc{FernandoDrescherDeubeletal.2018,
author = {Fernando, Raquel and Drescher, Cathleen and Deubel, Stefanie and Grune, Tilman and Castro, Jose Pedro},
title = {Distinct proteasomal activity for fast and slow twitch skeletal muscle during aging},
series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
volume = {120},
journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
publisher = {Elsevier},
address = {New York},
issn = {0891-5849},
doi = {10.1016/j.freeradbiomed.2018.04.393},
pages = {S119 -- S119},
year = {2018},
abstract = {Skeletal muscle alterations during aging lead to dysfunctional metabolism, correlating with frailty and early mortality. The loss of proteostasis is a hallmark of aging. Whether proteostasis loss plays a role in muscle aging remains elusive. To address this question we collected muscles, Soleus (SOL, type I) and Extensor digitorum longus (EDL, type II), from young (4 months) and old (25 months) C57BL/6 mice and evaluated the proteasomal system. Initial work showed decreased 26 S activity in old SOL. EDL displayed lower proteasomal activity in both ages compared to any of the SOL ages. Moreover, in order to understand if during aging there is the so-called "fiber switch from fast-to-slow", we performed western blots against sMHC and fMHC (slow and fast myosin heavy chain, respectively). Preliminary results suggest that young SOL is composed by slow twitch fibers but also contains fast twitch fibers, while young EDL seems to be mostly composed by fast twitch fibers that level down during aging, suggesting the switch. As a conclusion, EDL seems to have less proteasomal activity, however, if this is a contributor or a consequence to the muscle fiber switch during aging still needs further investigation.},
language = {en}
}
@misc{CastroGruneSpeckmann2017,
author = {Castro, Jos{\´e} Pedro and Grune, Tilman and Speckmann, Bodo},
title = {The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction},
url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-398039},
pages = {16},
year = {2017},
abstract = {White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho)physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e.g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance.},
language = {en}
}
@article{SpeckmannSchulzHilleretal.2017,
author = {Speckmann, Bodo and Schulz, Sarah and Hiller, Franziska and Hesse, Deike and Schumacher, Fabian and Kleuser, Burkhard and Geisel, Juergen and Obeid, Rima and Grune, Tilman and Kipp, Anna Patricia},
title = {Selenium increases hepatic DNA methylation and modulates one-carbon metabolism in the liver of mice},
series = {The journal of nutritional biochemistry},
volume = {48},
journal = {The journal of nutritional biochemistry},
publisher = {Elsevier},
address = {New York},
issn = {0955-2863},
doi = {10.1016/j.jnutbio.2017.07.002},
pages = {112 -- 119},
year = {2017},
abstract = {The average intake of the essential trace element selenium (Se) is below the recommendation in most European countries, possibly causing sub-optimal expression of selenoproteins. It is still unclear how a suboptimal Se status may affect health. To mimic this situation, mice were fed one of three physiologically relevant amounts of Se. We focused on the liver, the organ most sensitive to changes in the Se supply indicated by hepatic glutathione peroxidase activity. In addition, liver is the main organ for synthesis of methyl groups and glutathione via one-carbon metabolism. Accordingly, the impact of Se on global DNA methylation, methylation capacity, and gene expression was assessed. We observed higher global DNA methylation indicated by LINE1 methylation, and an increase of the methylation potential as indicated by higher S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio and by elevated mRNA expression of serine hydroxymethyltransferase in both or either of the Se groups. Furthermore, increasing the Se supply resulted in higher plasma concentrations of triglycerides. Hepatic expression of glycolytic and lipogenic genes revealed consistent Se dependent up-regulation of glucokinase. The sterol regulatory element-binding transcription factor 1 (Srebf1) was also up-regulated by Se. Both effects were confirmed in primary hepatocytes. In contrast to the overall Se-dependent increase of methylation capacity, the up-regulation of Srebf1 expression was paralleled by reduced local methylation of a specific CpG site within the Srebf1 gene. Thus, we provided evidence that Se-dependent effects on lipogenesis involve epigenetic mechanisms. (C) 2017 The Authors. Published by Elsevier Inc.},
language = {en}
}
@article{ReegJungCastroetal.2016,
author = {Reeg, Sandra and Jung, Tobias and Castro, Jos{\´e} Pedro and Davies, Kelvin J. A. and Henze, Andrea and Grune, Tilman},
title = {The molecular chaperone Hsp70 promotes the proteolytic removal of oxidatively damaged proteins by the proteasome},
series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
volume = {99},
journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
publisher = {Elsevier},
address = {New York},
issn = {0891-5849},
doi = {10.1016/j.freeradbiomed.2016.08.002},
pages = {153 -- 166},
year = {2016},
abstract = {One hallmark of aging is the accumulation of protein aggregates, promoted by the unfolding of oxidized proteins. Unraveling the mechanism by which oxidized proteins are degraded may provide a basis to delay the early onset of features, such as protein aggregate formation, that contribute to the aging phenotype. In order to prevent aggregation of oxidized proteins, cells recur to the 20S proteasome, an efficient turnover proteolysis complex. It has previously been shown that upon oxidative stress the 26S proteasome, another form, dissociates into the 20S form. A critical player implicated in its dissociation is the Heat Shock Protein 70 (Hsp70), which promotes an increase in free 20S proteasome and, therefore, an increased capability to degrade oxidized proteins. The aim of this study was to test whether or not Hsp70 is involved in cooperating with the 20S proteasome for a selective degradation of oxidatively damaged proteins. Our results demonstrate that Hsp70 expression is induced in HT22 cells as a result of mild oxidative stress conditions. Furthermore, Hsp70 prevents the accumulation of oxidized proteins and directly promotes their degradation by the 20S proteasome. In contrast the expression of the Heat shock cognate protein 70 (Hsc70) was not changed in recovery after oxidative stress and Hsc70 has no influence on the removal of oxidatively damaged proteins. We were able to demonstrate in HT22 cells, in brain homogenates from 129/SV mice and in vitro, that there is an increased interaction of Hsp70 with oxidized proteins, but also with the 20S proteasome, indicating a role of Hsp70 in mediating the interaction of oxidized proteins with the 20S proteasome. Thus, our data clearly implicate an involvement of Hsp70 oxidatively damaged protein degradation by the 20S proteasome. c) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).},
language = {en}
}
@misc{CastroGruneSpeckmann2016,
author = {Castro, Jos{\´e} Pedro and Grune, Tilman and Speckmann, Bodo},
title = {The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction},
series = {Biological chemistry},
volume = {397},
journal = {Biological chemistry},
publisher = {De Gruyter},
address = {Berlin},
issn = {1431-6730},
doi = {10.1515/hsz-2015-0305},
pages = {709 -- 724},
year = {2016},
abstract = {White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/ release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho) physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e. g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance.},
language = {en}
}
@misc{StuetzWeberDolleetal.2016,
author = {Stuetz, Wolfgang and Weber, Daniela and Doll{\´e}, Martijn E. T. and Jansen, Eug{\`e}ne and Grubeck-Loebenstein, Beatrix and Fiegl, Simone and Toussaint, Olivier and Bernhardt, Juergen and Gonos, Efstathios S. and Franceschi, Claudio and Sikora, Ewa and Moreno-Villanueva, Mar{\´i}a and Breusing, Nicolle and Grune, Tilman and B{\"u}rkle, Alexander},
title = {Plasma carotenoids, tocopherols, and retinol in the age-stratified (35-74 years) general population},
series = {Nutrients},
journal = {Nutrients},
url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-407659},
pages = {17},
year = {2016},
abstract = {Blood micronutrient status may change with age. We analyzed plasma carotenoids, α-/γ-tocopherol, and retinol and their associations with age, demographic characteristics, and dietary habits (assessed by a short food frequency questionnaire) in a cross-sectional study of 2118 women and men (age-stratified from 35 to 74 years) of the general population from six European countries. Higher age was associated with lower lycopene and α-/β-carotene and higher β-cryptoxanthin, lutein, zeaxanthin, α-/γ-tocopherol, and retinol levels. Significant correlations with age were observed for lycopene (r = -0.248), α-tocopherol (r = 0.208), α-carotene (r = -0.112), and β-cryptoxanthin (r = 0.125; all p < 0.001). Age was inversely associated with lycopene (-6.5\% per five-year age increase) and this association remained in the multiple regression model with the significant predictors (covariables) being country, season, cholesterol, gender, smoking status, body mass index (BMI (kg/m2)), and dietary habits. The positive association of α-tocopherol with age remained when all covariates including cholesterol and use of vitamin supplements were included (1.7\% vs. 2.4\% per five-year age increase). The association of higher β-cryptoxanthin with higher age was no longer statistically significant after adjustment for fruit consumption, whereas the inverse association of α-carotene with age remained in the fully adjusted multivariable model (-4.8\% vs. -3.8\% per five-year age increase). We conclude from our study that age is an independent predictor of plasma lycopene, α-tocopherol, and α-carotene.},
language = {en}
}