عرض بسيط للتسجيلة

المؤلفMajeed, Yasser
المؤلفHalabi, Najeeb
المؤلفMadani, Aisha Y
المؤلفEngelke, Rudolf
المؤلفBhagwat, Aditya M
المؤلفAbdesselem, Houari
المؤلفAgha, Maha V
المؤلفVakayil, Muneera
المؤلفCourjaret, Raphael
المؤلفGoswami, Neha
المؤلفHamidane, Hisham Ben
المؤلفElrayess, Mohamed A
المؤلفRafii, Arash
المؤلفGraumann, Johannes
المؤلفSchmidt, Frank
المؤلفMazloum, Nayef A
تاريخ الإتاحة2021-04-19T09:59:59Z
تاريخ النشر2021-04-01
اسم المنشورScientific Reports
المعرّفhttp://dx.doi.org/10.1038/s41598-021-87759-x
الاقتباسMajeed, 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
معرّف المصادر الموحدhttp://hdl.handle.net/10576/18285
الملخصThe 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.
اللغةen
الناشرNature Research
الموضوعEndocrine system and metabolic diseases
Endocrinology
Metabolism
العنوانSIRT1 promotes lipid metabolism and mitochondrial biogenesis in adipocytes and coordinates adipogenesis by targeting key enzymatic pathways.
النوعArticle
رقم العدد1
رقم المجلد11
ESSN2045-2322
dc.accessType Open Access


الملفات في هذه التسجيلة

Thumbnail

هذه التسجيلة تظهر في المجموعات التالية

عرض بسيط للتسجيلة