期刊
MOLECULAR CELL
卷 77, 期 4, 页码 810-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2019.12.003
关键词
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资金
- NIH [T32DK007203, T32AG029796, F32DK109556, L30DK110338, R01CA182543-S1, T32DK083250, R01DK053189, R01DK098203, R01AG055452, R01DK108790, R01DK114401]
- University of Minnesota [E-0917-2]
- American Diabetes Association [1-16-IBS-203]
Lipid droplets (LDs) provide a reservoir for triacylglycerol storage and are a central hub for fatty acid trafficking and signaling in cells. Lipolysis promotes mitochondrial biogenesis and oxidative metabolism via a SIRT1/PGC-1 alpha/PPAR alpha-dependent pathway through an unknown mechanism. Herein, we identify that monounsaturated fatty acids (MUFAs) allosterically activate SIRT1 toward select peptide-substrates such as PGC-1 alpha. MUFAs enhance PGC-1 alpha/PPARa alpha signaling and promote oxidative metabolism in cells and animal models in a SIRT1-dependent manner. Moreover, we characterize the LD protein perilipin 5 (PLIN5), which is known to enhance mitochondrial biogenesis and function, to be a fattyacid-binding protein that preferentially binds LD-derived monounsaturated fatty acids and traffics them to the nucleus following cAMP/PKA-mediated lipolytic stimulation. Thus, these studies identify the first-known endogenous allosteric modulators of SIRT1 and characterize a LD-nuclear signaling axis that underlies the known metabolic benefits of MUFAs and PLIN5.
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