TY  - THES
A1  - Radloff, Katrin
T1  - The role of the fatty acid profile and its modulation by cytokines in the systemic inflammation in cancer cachexia
T1  - O papel e a modulação do perfil de ácidos graxos por citocinas na inflamação da caquexia associada ao câncer
T1  - Die Rolle des Fettsäure-Profils und dessen entzündungsbedingten Veränderungen in der Tumorkachexie
N2  - Systemic inflammation is a hallmark of cancer cachexia. Among tumor-host interactions, the white adipose tissue (WAT) is an important contributor to inflammation as it suffers morphological reorganization and lipolysis, releasing free fatty acids (FA), bioactive lipid mediators (LM) and pro-inflammatory cytokines, which accentuate the activation of pro-inflammatory signaling pathways and the recruitment of immune cells to the tissue. This project aimed to investigate which inflammatory factors are involved in the local adipose tissue inflammation and what is the influence of such factors upon enzymes involved in FA or LM metabolism in healthy individuals (Control), weight stable gastro-intestinal cancer patients (WSC) and cachectic cancer patients (CC). The results demonstrated that the inflammatory signature of systemic inflammation is different from local adipose tissue inflammation. The systemic inflammation of the cachectic cancer patients was characterized by higher levels of circulating saturated fatty acids (SFA), tumor-necrosis-factor-α (TNF-α), interleukins IL-6, IL-8 and CRP while levels of polyunsaturated fatty acids (PUFAs), especially n3-PUFAs, were lower in CC than in the other groups. In vitro and in adipose tissue explants, pro-inflammatory cytokines and SFAs were shown to increase the chemokines IL-8 and CXCL10 that were found to be augmented in adipose tissue inflammation in CC which was more profound in the visceral adipose tissue (VAT) than in subcutaneous adipose tissue (SAT). Systemic inflammation was negatively associated with the expression of PUFA synthesizing enzymes, though gene and protein expression did hardly differ between groups. The effects of inflammatory factors on enzymes in the whole tissue could have been masked by differentiated modulation of the diverse cell types in the same tissue. In vitro experiments showed that the expression of FA-modifying enzymes such as desaturases and elongases in adipocytes and macrophages was regulated into opposing directions by TNF-α, IL-6, LPS or palmitate. The higher plasma concentration of the pro-resolving LM resolvin D1 in CC cannot compensate the overall inflammatory status and the results indicate that inflammatory cytokines interfere with synthesis pathways of pro-resolving LM. In summary, the data revealed a complex inter-tissue and inter-cellular crosstalk mediated by pro-inflammatory cytokines and lipid compounds enhancing inflammation in cancer cachexia by feed-forward mechanisms.
N2  - Systemische Entzündung ist ein grundlegendes Merkmal der Tumorkachexie. Bei den entzündungstreibenden Wechselwirkungen zwischen Tumor und Wirt spielt das weiße Fettgewebe eine besondere Rolle, da es, bedingt durch morphologische Veränderungen und Lipolyse, freie Fettsäuren, bioaktive Lipidmediatoren (LM) und pro-inflammatorische Cytokine freisetzt. Diese verschiedenen Substanzen verstärken die Aktivierung entzündungsfördernder Signalwege und eine Rekrutierung von Immunzellen in das Gewebe. Das Ziel dieser Arbeit war es daher zu untersuchen, welche Faktoren an der Entwicklung der lokalen Fettgewebsentzündung beteiligt sind und wie diese Faktoren Syntheseenzyme von Fettsäuren und Lipidmediatoren beeinflussen könnten. Dazu wurden Plasma und Fettgewebeproben von gesunden Kontrollpersonen (Control) und normalgewichtigen (WSC) sowie kachektischen Magen-Darm-Krebs-Patienten (CC) untersucht. Die Ergebnisse zeigten, dass sich die inflammatorischen Charakteristiken der systemischen Entzündung von denen der lokalen Fettgewebsentzündung unterscheiden. Die systemische Entzündung war gekennzeichnet durch höhere Spiegel gesättigter Fettsäuren (SFA), Tumor-necrosis-factor alpha (TNF-α), Interleukin IL-6, IL-8 und C-reactive protein (CRP) während die Konzentrationen von mehrfachungesättigten Fettsäuren (PUFA) –besonders n3-Fettsäuren- geringer in CC waren als in den anderen Gruppen. In vitro und in ex vivo kultivierten Fettgewebssegmenten konnte gezeigt werden, dass die Inkubation mit pro-inflammatorischen Cytokinen und gesättigten Fettsäuren zu einem Anstieg der Chemokine IL-8 sowie CXCL10 führte. Erhöhte Spiegel dieser Moleküle wurden auch in der Fettgewebsentzündung bei kachektischen Patienten beobachtet, welche im viszeralen Fettgewebe ausgeprägter war als im subkutanen. Systemische Entzündungsmarker waren negativ mit der Expression PUFA-synthetisierender Enzyme assoziiert, obwohl sich Gesamt-mRNA-sowie Proteingehalt kaum zwischen den Studiengruppen unterschieden. Die Effekte von Entzündungsfaktoren auf diese Enzyme im Gesamtgewebe könnten durch eine differenzielle Modulierung in diversen Zelltypen des Gewebes maskiert sein. Denn in in vitro-Experimenten zeigte die Inkubation mit TNF-α, IL-6, LPS oder Palmitat, dass die GeneExpression von Fettsäure-modifizierenden Enzymen wie Desaturasen oder Elongasen in Adipozyten und Makrophagen in entgegengesetzte Richtungen reguliert wird. Die höhere Plasmakonzentration des entzündungslösenden LM Resolvin D1 in CC konnte dem inflammatorischen Zustand nicht entgegenwirken und die Ergebnisse deuten darauf hin, dass inflammatorische Cytokine in die Synthesewege von entzündungslösenden LM eingreifen. Zusammenfassend demonstrieren die Daten das komplexe Zusammenspiel zwischen verschiedenen Geweben und Zelltypen, in dem Cytokine und Lipidverbindungen aus dem Blutkreislauf die Entzündung der Tumorkachexie durch selbst-verstärkende Mechanismen vorantreiben.
N2  - A inflamação sistêmica é uma das características que marcam o diagnóstico da caquexia associada ao câncer. Entre as interações tumor-hospedeiro, o tecido adiposo branco contribui à inflamação, uma vez que ele sofre uma reorganização morfológica e lipólise, liberando ácidos graxos livres (AGLs), mediadores lipídicos (LMs) e citocinas pró-inflamatórias, que acentuam a ativação de vias de sinalização pró-inflamatória e o recrutamento de células do sistema imunológico para o tecido. O objetivo deste projeto foi investigar quais fatores inflamatórios sistêmicos estão envolvidos na inflamação do tecido adiposo e qual é a influência desses fatores sobre as enzimas envolvidas no metabolismo dos AGs ou LMs em indivíduos saudáveis (Controle), pacientes com câncer gastrointestinal com peso estável (WSC) e pacientes com câncer e caquexia (CC). Os resultados demonstraram que a resposta inflamatória sistêmica é diferente da resposta encontrada no tecido adiposo. A inflamação sistêmica dos pacientes com câncer e caquexia (CC) foi caracterizada por níveis circulantes mais elevados de ácidos graxos saturados (SFAs), tumor-necrosis-factor-α (TNF-α), Interleukin IL-6, IL-8 e proteina C-reativa (PCR), enquanto os níveis de ácidos graxos poliinsaturados (PUFAs), especialmente n3-PUFAs, foram menores em CC que nos demais grupos. In vitro e em explantes de tecido adiposo, citocinas pró-inflamatórias e SFAs aumentaram a expressão das quimiocinas IL-8 e CXCL10. E tambêm observamos um aumento na expressão destas quimiocinas na inflamação do tecido adiposo no CC, que era mais profundo no tecido adiposo visceral (VAT) quando comparado ao tecido adiposo subcutâneo (SAT). A inflamação sistêmica foi negativamente associada com a expressão de enzimas sintetizadoras dos PUFAs, embora a expressão gênica e protéica mostraram somente pequenas diferencias entre os grupos. Os efeitos dos fatores inflamatórios sobre as enzimas no tecido adiposo podem ter sido mascarados pela modulação diferenciada dos diversos tipos celulares constituintes desse tecido. Experimentos in vitro mostraram que a expressão de enzimas que modificam os AGs, tais como as dessaturases e elongases em adipócitos e macrófagos, foram reguladas em direções opostas por TNF-α, IL-6, LPS e palmitato. Mesmo os pacientes CC demonstrando uma maior concentração plasmática da Resolvina D1, que é um mediador lipídico de resolução da inflamação, ainda assim, a inflamação sistêmica é maior nesses pacientes, e os resultados indicam que as citoquinas inflamatórias interferem com as vias de síntese das LMs da resolução. Concluímos que, os dados revelaram um crosstalk inter-tecidual e intercelular complexo mediado por citocinas pró-inflamatórias e compostos lipídicos que aumentam a inflamação na caquexia associada ao câncer por mecanismos autoregulação.
KW  - cancer cachexia
KW  - inflammation
KW  - adipose tissue
KW  - cytokines
KW  - chemokines
KW  - SFA
KW  - PUFA
Y1  - 2018
ER  - 
TY  - JOUR
A1  - Musalek, Martin
A1  - Kokstejn, Jakub
A1  - Papez, Pavel
A1  - Scheffler, Christiane
A1  - Mumm, Rebekka
A1  - Czernitzki, Anna-Franziska
A1  - Koziel, Slawomir
T1  - Impact of normal weight obesity on fundamental motor skills in pre-school children aged 3 to 6 years
JF  - Journal of biological and clinical anthropology : Anthropologischer Anzeiger ; Mitteilungsorgan der Gesellschaft für Anthropologie
N2  - Normal weight obesity is defined as having excessive body fat, but normal BMI. Even though previous research revealed that excessive body fat in children inhibited their physical activity and decreased motor performance, there has been only little evidence about motor performance of normal weight obese children. This study aims to establish whether normal weight obese pre-school children aged 3-6 years will have a significantly worse level of fundamental motor skills compared to normal weight non-obese counterparts. The research sample consisted of 152 pre-schoolers selected from a specific district of Prague, the Czech Republic. According to values from four skinfolds: triceps, subscapula, suprailiaca, calf, and BMI three categories of children aged 3-6 years were determined: A) normal weight obese n = 51; B) normal weight non-obese n = 52; C) overweight and obese n = 49. The Movement Assessment Battery for Children (MABC-2) was used for the assessment of fundamental motor skills. Normal weight obese children had significantly higher amount of adipose tissue p < 0.001 than normal weight non-obese children but the same average BMI. Moreover, normal weight obese children did not have significantly less amount of subcutaneous fat on triceps and calf compared to their overweight and obese peers. In majority of MABC-2 tests, normal weight obese pre-schoolers showed the poorest performance. Moreover, normal weight obese children had significantly worse total standard score = 38.82 compared to normal weight non-obese peers = 52.27; p < 0.05. In addition, normal weight obese children had a more than three times higher frequency OR = 3.69 CI95% (1.10; 12.35) of severe motor deficit performance <= 5th centile of the MABC-2 norm. These findings are strongly alarming since indices like BMI are not able to identify normal weight obese individual. We recommend verifying real portion of normal weight obese children as they are probably in higher risk of health and motor problems than overweight and obese population due to their low lean mass.
KW  - normal weight obesity
KW  - fundamental motor skills
KW  - MABC-2
KW  - performance
KW  - pre-school children
KW  - skinfolds
KW  - adipose tissue
KW  - lean mass
Y1  - 2017
U6  - https://doi.org/10.1127/anthranz/2017/0752
SN  - 0003-5548
VL  - 74
SP  - 203
EP  - 212
PB  - Schweizerbart
CY  - Stuttgart
ER  - 
TY  - THES
A1  - Mancini, Carola
T1  - Analysis of the effects of age-related changes of metabolic flux on brown adipocyte formation and function
N2  - Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, thereby allowing mammals to maintain a constant body temperature in a cold environment. Thermogenic capacity of this tissue is due to a high mitochondrial density and expression of uncoupling protein 1 (UCP1), a unique brown adipocyte marker which dissipates the mitochondrial proton gradient to produce heat instead of ATP. BAT is actively involved in whole-body metabolic homeostasis and during aging there is a loss of classical brown adipose tissue with concomitantly reduced browning capacity of white adipose tissue. Therefore, an age-dependent decrease of BAT-related energy expenditure capacity may exacerbate the development of metabolic diseases, including obesity and type 2 diabetes mellitus. Given that direct effects of age-related changes of BAT-metabolic flux have yet to be unraveled, the aim of the current thesis is to investigate potential metabolic mechanisms involved in BAT-dysfunction during aging and to identify suitable metabolic candidates as functional biomarkers of BAT-aging. To this aim, integration of transcriptomic, metabolomic and proteomic data analyses of BAT from young and aged mice was performed, and a group of candidates with age-related changes was revealed. Metabolomic analysis showed age-dependent alterations of metabolic intermediates involved in energy, nucleotide and vitamin metabolism, with major alterations regarding the purine nucleotide pool. These data suggest a potential role of nucleotide intermediates in age-related BAT defects. In addition, the screening of transcriptomic and proteomic data sets from BAT of young and aged mice allowed identification of a 60-kDa lysophospholipase, also known as L-asparaginase (Aspg), whose expression declines during BAT-aging. Involvement of Aspg in brown adipocyte thermogenic function was subsequently analyzed at the molecular level using in vitro approaches and animal models. The findings revealed sensitivity of Aspg expression to β3-adrenergic activation via different metabolic cues, including cold exposure and treatment with β3-adrenergic agonist CL. To further examine ASPG function in BAT, an over-expression model of Aspg in a brown adipocyte cell line was established and showed that these cells were metabolically more active compared to controls, revealing increased expression of the main brown-adipocyte specific marker UCP1, as well as higher lipolysis rates. An in vitro loss-of-function model of Aspg was also functionally analyzed, revealing reduced brown adipogenic characteristics and an impaired lipolysis, thus confirming physiological relevance of Aspg in brown adipocyte function. Characterization of a transgenic mouse model with whole-body inactivation of the Aspg gene (Aspg-KO) allowed investigation of the role of ASPG under in vivo conditions, indicating a mild obesogenic phenotype, hypertrophic white adipocytes, impairment of the early thermogenic response upon cold-stimulation and dysfunctional insulin sensitivity. Taken together, these data show that ASPG may represent a new functional biomarker of BAT-aging that regulates thermogenesis and therefore a potential target for the treatment of age-related metabolic disease.
KW  - adipose tissue
KW  - aging
KW  - nutrients
KW  - metabolism
KW  - Fettgewebe
KW  - Alterung
KW  - Stoffwechsel
KW  - Nährstoffe
Y1  - 2021
U6  - https://doi.org/10.25932/publishup-51266
ER  - 
TY  - JOUR
A1  - Krstic, Jelena
A1  - Reinisch, Isabel
A1  - Schupp, Michael
A1  - Schulz, Tim Julius
A1  - Prokesch, Andreas
T1  - p53 functions in adipose tissue metabolism and homeostasis
JF  - International journal of molecular sciences
N2  - As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue-and cell-specific actions of p53 and its downstream signaling pathways. In this review, we focus on studies reporting p53's impact on adipocyte development, function, and maintenance, as well as the causes and consequences of altered p53 levels in white and brown adipose tissue (AT) with respect to systemic energy homeostasis. While whole body p53 knockout mice gain less weight and fat mass under a high-fat diet owing to increased energy expenditure, modifying p53 expression specifically in adipocytes yields more refined insights: (1) p53 is a negative regulator of in vitro adipogenesis; (2) p53 levels in white AT are increased in diet-induced and genetic obesity mouse models and in obese humans; (3) functionally, elevated p53 in white AT increases senescence and chronic inflammation, aggravating systemic insulin resistance; (4) p53 is not required for normal development of brown AT; and (5) when p53 is activated in brown AT in mice fed a high-fat diet, it increases brown AT temperature and brown AT marker gene expression, thereby contributing to reduced fat mass accumulation. In addition, p53 is increasingly being recognized as crucial player in nutrient sensing pathways. Hence, despite existence of contradictory findings and a varying density of evidence, several functions of p53 in adipocytes and ATs have been emerging, positioning p53 as an essential regulatory hub in ATs. Future studies need to make use of more sophisticated in vivo model systems and should identify an AT-specific set of p53 target genes and downstream pathways upon different (nutrient) challenges to identify novel therapeutic targets to curb metabolic diseases
KW  - p53
KW  - adipose tissue
KW  - metabolic syndrome
KW  - obesity
KW  - adipogenesis
KW  - insulin resistance
Y1  - 2018
U6  - https://doi.org/10.3390/ijms19092622
SN  - 1422-0067
VL  - 19
IS  - 9
PB  - MDPI
CY  - Basel
ER  - 
TY  - GEN
A1  - Krstic, Jelena
A1  - Reinisch, Isabel
A1  - Schupp, Michael
A1  - Schulz, Tim Julius
A1  - Prokesch, Andreas
T1  - p53 functions in adipose tissue metabolism and homeostasis
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue-and cell-specific actions of p53 and its downstream signaling pathways. In this review, we focus on studies reporting p53's impact on adipocyte development, function, and maintenance, as well as the causes and consequences of altered p53 levels in white and brown adipose tissue (AT) with respect to systemic energy homeostasis. While whole body p53 knockout mice gain less weight and fat mass under a high-fat diet owing to increased energy expenditure, modifying p53 expression specifically in adipocytes yields more refined insights: (1) p53 is a negative regulator of in vitro adipogenesis; (2) p53 levels in white AT are increased in diet-induced and genetic obesity mouse models and in obese humans; (3) functionally, elevated p53 in white AT increases senescence and chronic inflammation, aggravating systemic insulin resistance; (4) p53 is not required for normal development of brown AT; and (5) when p53 is activated in brown AT in mice fed a high-fat diet, it increases brown AT temperature and brown AT marker gene expression, thereby contributing to reduced fat mass accumulation. In addition, p53 is increasingly being recognized as crucial player in nutrient sensing pathways. Hence, despite existence of contradictory findings and a varying density of evidence, several functions of p53 in adipocytes and ATs have been emerging, positioning p53 as an essential regulatory hub in ATs. Future studies need to make use of more sophisticated in vivo model systems and should identify an AT-specific set of p53 target genes and downstream pathways upon different (nutrient) challenges to identify novel therapeutic targets to curb metabolic diseases.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1047 
KW  - p53
KW  - adipose tissue
KW  - metabolic syndrome
KW  - obesity
KW  - adipogenesis
KW  - insulin resistance
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-469069
SN  - 1866-8372
IS  - 1047
ER  - 
TY  - JOUR
A1  - Hauffe, Robert
A1  - Rath, Michaela
A1  - Agyapong, Wilson
A1  - Jonas, Wenke
A1  - Vogel, Heike
A1  - Schulz, Tim Julius
A1  - Schwarz, Maria
A1  - Kipp, Anna Patricia
A1  - Blüher, Matthias
A1  - Kleinridders, André
T1  - Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling
JF  - Antioxidants
N2  - The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.
KW  - selenite
KW  - insulin
KW  - adipose tissue
KW  - obesity
KW  - insulin resistance
Y1  - 2022
U6  - https://doi.org/10.3390/antiox11050862
SN  - 2076-3921
VL  - 11
SP  - 1
EP  - 16
PB  - MDPI
CY  - Basel, Schweiz
ET  - 5
ER  - 
TY  - GEN
A1  - Hauffe, Robert
A1  - Rath, Michaela
A1  - Agyapong, Wilson
A1  - Jonas, Wenke
A1  - Vogel, Heike
A1  - Schulz, Tim Julius
A1  - Schwarz, Maria
A1  - Kipp, Anna Patricia
A1  - Blüher, Matthias
A1  - Kleinridders, André
T1  - Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling
T2  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1267 
KW  - selenite
KW  - insulin
KW  - adipose tissue
KW  - obesity
KW  - insulin resistance
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-561709
SN  - 1866-8372
SP  - 1
EP  - 16
PB  - Universitätsverlag Potsdam
CY  - Potsdam
ER  - 
TY  - JOUR
A1  - Graja, Antonia
A1  - Garcia-Carrizo, Francisco
A1  - Jank, Anne-Marie
A1  - Gohlke, Sabrina
A1  - Ambrosi, Thomas H.
A1  - Jonas, Wenke
A1  - Ussar, Siegfried
A1  - Kern, Matthias
A1  - Schürmann, Annette
A1  - Aleksandrova, Krasimira
A1  - Bluher, Matthias
A1  - Schulz, Tim Julius
T1  - Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism
JF  - Aging Cell
N2  - Remodeling of the extracellular matrix is a key component of the metabolic adaptations of adipose tissue in response to dietary and physiological challenges. Disruption of its integrity is a well-known aspect of adipose tissue dysfunction, for instance, during aging and obesity. Adipocyte regeneration from a tissue-resident pool of mesenchymal stem cells is part of normal tissue homeostasis. Among the pathophysiological consequences of adipogenic stem cell aging, characteristic changes in the secretory phenotype, which includes matrix-modifying proteins, have been described. Here, we show that the expression of the matricellular protein periostin, a component of the extracellular matrix produced and secreted by adipose tissue-resident interstitial cells, is markedly decreased in aged brown and white adipose tissue depots. Using a mouse model, we demonstrate that the adaptation of adipose tissue to adrenergic stimulation and high-fat diet feeding is impaired in animals with systemic ablation of the gene encoding for periostin. Our data suggest that loss of periostin attenuates lipid metabolism in adipose tissue, thus recapitulating one aspect of age-related metabolic dysfunction. In human white adipose tissue, periostin expression showed an unexpected positive correlation with age of study participants. This correlation, however, was no longer evident after adjusting for BMI or plasma lipid and liver function biomarkers. These findings taken together suggest that age-related alterations of the adipose tissue extracellular matrix may contribute to the development of metabolic disease by negatively affecting nutrient homeostasis.
KW  - adipogenic progenitor cells
KW  - adipose tissue
KW  - aging
KW  - extracellular matrix
KW  - fatty acid metabolism
KW  - periostin
Y1  - 2018
U6  - https://doi.org/10.1111/acel.12810
SN  - 1474-9718
SN  - 1474-9726
VL  - 17
IS  - 5
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Gohlke, Sabrina
A1  - Mancini, Carola
A1  - Garcia-Carrizo, Francisco
A1  - Schulz, Tim J.
T1  - Loss of the ciliary gene Bbs4 results in defective thermogenesis due to metabolic inefficiency and impaired lipid metabolism
JF  - The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology
N2  - Adipose tissue is central to the regulation of energy balance. While white adipose tissue (WAT) is responsible for triglyceride storage, brown adipose tissue specializes in energy expenditure. Deterioration of brown adipocyte function contributes to the development of metabolic complications like obesity and diabetes. These disorders are also leading symptoms of the Bardet-Biedl syndrome (BBS), a hereditary disorder in humans which is caused by dysfunctions of the primary cilium and which therefore belongs to the group of ciliopathies. The cilium is a hair-like organelle involved in cellular signal transduction. The BBSome, a supercomplex of several Bbs gene products, localizes to the basal body of cilia and is thought to be involved in protein sorting to and from the ciliary membrane. The effects of a functional BBSome on energy metabolism and lipid mobilization in brown and white adipocytes were tested in whole-body Bbs4 knockout mice that were subjected to metabolic challenges. Chronic cold exposure reveals cold-intolerance of knockout mice but also ameliorates the markers of metabolic pathology detected in knockouts prior to cold. Hepatic triglyceride content is markedly reduced in knockout mice while circulating lipids are elevated, altogether suggesting that defective lipid metabolism in adipose tissue creates increased demand for systemic lipid mobilization to meet energetic demands of reduced body temperatures. These findings taken together suggest that Bbs4 is essential for the regulation of adipose tissue lipid metabolism, representing a potential target to treat metabolic disorders.
KW  - adipose tissue
KW  - Bbs4
KW  - BBsome
KW  - browning
KW  - cilium
KW  - lipid metabolism
Y1  - 2021
U6  - https://doi.org/10.1096/fj.202100772RR
SN  - 1530-6860
VL  - 35
IS  - 11
PB  - Wiley
CY  - Hoboken
ER  -