49222
2019
2019
eng
1
17
17
24
article
Elsevier
Amsterdam
1
2019-04-04
--
--
Identification of functional lipid metabolism biomarkers of brown adipose tissue aging
Objective: Aging is accompanied by loss of brown adipocytes and a decline in their thermogenic potential, which may exacerbate the development of adiposity and other metabolic disorders. Presently, only limited evidence exists describing the molecular alterations leading to impaired brown adipogenesis with aging and the contribution of these processes to changes of systemic energy metabolism.
Methods: Samples of young and aged murine brown and white adipose tissue were used to compare age-related changes of brown adipogenic gene expression and thermogenesis-related lipid mobilization. To identify potential markers of brown adipose tissue aging, non-targeted proteomic and metabolomic as well as targeted lipid analyses were conducted on young and aged tissue samples. Subsequently, the effects of several candidate lipid classes on brown adipocyte function were examined.
Results: Corroborating previous reports of reduced expression of uncoupling protein-1, we observe impaired signaling required for lipid mobilization in aged brown fat after adrenergic stimulation. Omics analyses additionally confirm the age-related impairment of lipid homeostasis and reveal the accumulation of specific lipid classes, including certain sphingolipids, ceramides, and dolichols in aged brown fat. While ceramides as well as enzymes of dolichol metabolism inhibit brown adipogenesis, inhibition of sphingosine 1-phosphate receptor 2 induces brown adipocyte differentiation.
Conclusions: Our functional analyses show that changes in specific lipid species, as observed during aging, may contribute to reduced thermogenic potential. They thus uncover potential biomarkers of aging as well as molecular mechanisms that could contribute to the degradation of brown adipocytes, thereby providing potential treatment strategies of age-related metabolic conditions.
Molecular Metabolism
10.1016/j.molmet.2019.03.011
31003944
2212-8778
wos:2019
WOS:000468472300001
Schulz, TJ (reprint author), German Inst Human Nutr, D-14558 Potsdam, Germany., tim.schulz@dife.de
German Research Foundation (DFG)German Research Foundation (DFG) [SCHU 2445/2-1, SCHU 2445/5-1]; European Research CouncilEuropean Research Council (ERC) [ERC-StG 311082]; Paul Ehrlich Foundation; German Ministry of Education and Research (BMBF)Federal Ministry of Education & Research (BMBF); State of Brandenburg (DZD) [82DZD00302, FKZ 82DZD0038G]; NutriAct -Competence Cluster Nutrition Research Berlin-Potsdam - Federal Ministry of Education and Research [FKZ: 01EA1408A-G]
2021-02-03T08:26:16+00:00
sword
importub
filename=package.tar
e06ec72751683c43d71a0bea272ec791
Schulz, Tim Julius
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true
CC-BY - Namensnennung 4.0 International
Sabrina Gohlke
Vyacheslav Zagoriy
Alvaro Cuadros Inostroza
Michael Meret
Carola Mancini
Lukasz Japtok
Fabian Schumacher
Doreen Kuhlow
Antonia Graja
Heike Stephanowitz
Markus Jähnert
Eberhard Krause
Andreas Wernitz
Klaus-Juergen Petzke
Annette Schürmann
Burkhard Kleuser
Tim Julius Schulz
eng
uncontrolled
Brown adipose tissue
eng
uncontrolled
Aging
eng
uncontrolled
Ceramides
eng
uncontrolled
Sphingolipids
eng
uncontrolled
Dolichol lipids
Medizin und Gesundheit
Institut für Ernährungswissenschaft
Referiert
Import
Gold Open-Access
DOAJ gelistet
38221
2014
2014
eng
134
147
14
1
34
review
Karger
Basel
1
--
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Divergent role of sphingosine 1-Phosphate on insulin resistance
Insulin resistance is a complex metabolic disorder in which insulin-sensitive tissues fail to respond to the physiological action of insulin. There is a strong correlation of insulin resistance and the development of type 2 diabetes both reaching epidemic proportions. Dysfunctional lipid metabolism is a hallmark of insulin resistance and a risk factor for several cardiovascular and metabolic disorders. Numerous studies in humans and rodents have shown that insulin resistance is associated with elevations of non-esterified fatty acids (NEFA) in the plasma. Moreover, bioactive lipid intermediates such as diacylglycerol (DAG) and ceramides appear to accumulate in response to NEFA, which may interact with insulin signaling. However, recent work has also indicated that sphingosine 1-phosphate (S1P), a breakdown product of ceramide, modulate insulin signaling in different cell types. In this review, we summarize the current state of knowledge about S1P and insulin signaling in insulin sensitive cells. A specific focus is put on the action of S1P on hepatocytes, pancreatic beta-cells and skeletal muscle cells. In particular, modulation of S1P-signaling can be considered as a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes.
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
10.1159/000362990
24977487
1015-8987
1421-9778
wos:2014
WOS:000343764000011
Kleuser, B (reprint author), Univ Potsdam, Fac Math & Nat Sci, Inst Nutr Sci, Dept Toxicol, Arthur Scheunert Allee 114-116, D-14558 Potsdam, Germany., kleuser@uni-potsdam.de
Deutsche Forschungsgemeinschaft (DFG) [KL988/4-4]
Susann Fayyaz
Lukasz Japtok
Burkhard Kleuser
eng
uncontrolled
Sphingosine 1-phosphate (S1P)
eng
uncontrolled
Insulin resistance
eng
uncontrolled
Ceramides
eng
uncontrolled
Diacylglycerol (DAG)
eng
uncontrolled
Non-esterified fatty acids (NEFA)
eng
uncontrolled
Hepatocytes
eng
uncontrolled
Pancreatic cells
eng
uncontrolled
Skeletal muscle cells
Institut für Ernährungswissenschaft
Referiert
Open Access