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AuthorMajeed, Yasser
AuthorHalabi, Najeeb
AuthorMadani, Aisha Y
AuthorEngelke, Rudolf
AuthorBhagwat, Aditya M
AuthorAbdesselem, Houari
AuthorAgha, Maha V
AuthorVakayil, Muneera
AuthorCourjaret, Raphael
AuthorGoswami, Neha
AuthorHamidane, Hisham Ben
AuthorElrayess, Mohamed A
AuthorRafii, Arash
AuthorGraumann, Johannes
AuthorSchmidt, Frank
AuthorMazloum, Nayef A
Available date2021-04-19T09:59:59Z
Publication Date2021-04-01
Publication NameScientific Reports
Identifierhttp://dx.doi.org/10.1038/s41598-021-87759-x
CitationMajeed, Y., Halabi, N., Madani, A.Y. et al. SIRT1 promotes lipid metabolism and mitochondrial biogenesis in adipocytes and coordinates adipogenesis by targeting key enzymatic pathways. Sci Rep 11, 8177 (2021). https://doi.org/10.1038/s41598-021-87759-x
URIhttp://hdl.handle.net/10576/18285
AbstractThe NAD-dependent deacetylase SIRT1 controls key metabolic functions by deacetylating target proteins and strategies that promote SIRT1 function such as SIRT1 overexpression or NAD boosters alleviate metabolic complications. We previously reported that SIRT1-depletion in 3T3-L1 preadipocytes led to C-Myc activation, adipocyte hyperplasia, and dysregulated adipocyte metabolism. Here, we characterized SIRT1-depleted adipocytes by quantitative mass spectrometry-based proteomics, gene-expression and biochemical analyses, and mitochondrial studies. We found that SIRT1 promoted mitochondrial biogenesis and respiration in adipocytes and expression of molecules like leptin, adiponectin, matrix metalloproteinases, lipocalin 2, and thyroid responsive protein was SIRT1-dependent. Independent validation of the proteomics dataset uncovered SIRT1-dependence of SREBF1c and PPARα signaling in adipocytes. SIRT1 promoted nicotinamide mononucleotide acetyltransferase 2 (NMNAT2) expression during 3T3-L1 differentiation and constitutively repressed NMNAT1 and 3 levels. Supplementing preadipocytes with the NAD booster nicotinamide mononucleotide (NMN) during differentiation increased expression levels of leptin, SIRT1, and PGC-1α and its transcriptional targets, and reduced levels of pro-fibrotic collagens (Col6A1 and Col6A3) in a SIRT1-dependent manner. Investigating the metabolic impact of the functional interaction of SIRT1 with SREBF1c and PPARα and insights into how NAD metabolism modulates adipocyte function could potentially lead to new avenues in developing therapeutics for obesity complications.
Languageen
PublisherNature Research
SubjectEndocrine system and metabolic diseases
Endocrinology
Metabolism
TitleSIRT1 promotes lipid metabolism and mitochondrial biogenesis in adipocytes and coordinates adipogenesis by targeting key enzymatic pathways.
TypeArticle
Issue Number1
Volume Number11
ESSN2045-2322
dc.accessType Open Access


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