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
- 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 brownObjective: 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.…
MetadatenAuthor details: | Sabrina Gohlke, Vyacheslav Zagoriy, Alvaro Cuadros Inostroza, Michael Meret, Carola ManciniORCiD, Lukasz JaptokGND, Fabian SchumacherORCiDGND, Doreen Kuhlow, Antonia GrajaGND, Heike Stephanowitz, Markus JähnertORCiD, Eberhard Krause, Andreas Wernitz, Klaus-Juergen Petzke, Annette SchürmannORCiDGND, Burkhard KleuserORCiDGND, Tim Julius SchulzORCiDGND |
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DOI: | https://doi.org/10.1016/j.molmet.2019.03.011 |
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ISSN: | 2212-8778 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/31003944 |
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Title of parent work (English): | Molecular Metabolism |
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Publisher: | Elsevier |
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Place of publishing: | Amsterdam |
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Publication type: | Article |
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Language: | English |
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Year of first publication: | 2019 |
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Publication year: | 2019 |
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Release date: | 2021/02/03 |
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Tag: | Aging; Brown adipose tissue; Ceramides; Dolichol lipids; Sphingolipids |
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Volume: | 24 |
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Number of pages: | 17 |
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First page: | 1 |
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Last Page: | 17 |
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Funding institution: | 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] |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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DDC classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Peer review: | Referiert |
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Publishing method: | Open Access / Gold Open-Access |
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| DOAJ gelistet |
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License (German): | CC-BY - Namensnennung 4.0 International |
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