Program in Molecular Medicine; Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes; UMass Metabolic Network
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
BACKGROUND: The de novo biosynthesis of fatty acids (DNL) through fatty acid synthase (FASN) in adipocytes is exquisitely regulated by nutrients, hormones, fasting, and obesity in mice and humans. However, the functions of DNL in adipocyte biology and in the regulation of systemic glucose homeostasis are not fully understood.
METHODS and RESULTS: Here we show adipocyte DNL controls crosstalk to localized sympathetic neurons that mediate expansion of beige/brite adipocytes within inguinal white adipose tissue (iWAT). Induced deletion of FASN in white and brown adipocytes of mature mice (iAdFASNKO mice) enhanced glucose tolerance, UCP1 expression, and cAMP signaling in iWAT. Consistent with induction of adipose sympathetic nerve activity, iAdFASNKO mice displayed markedly increased neuronal tyrosine hydroxylase (TH) and neuropeptide Y (NPY) content in iWAT. In contrast, brown adipose tissue (BAT) of iAdFASNKO mice showed no increase in TH or NPY, nor did FASN deletion selectively in brown adipocytes (UCP1-FASNKO mice) cause these effects in iWAT.
CONCLUSIONS: These results demonstrate that downregulation of fatty acid synthesis via FASN depletion in white adipocytes of mature mice can stimulate neuronal signaling to control thermogenic programming in iWAT.
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Copyright © 2017 The Authors. Citation: Mol Metab. 2017 May 31;6(8):781-796. doi: 10.1016/j.molmet.2017.05.012. eCollection 2017 Aug. Link to article on publisher's site
Adipocytes, de novo lipogenesis, iWAT browning, Glucose homeostasis, ssympathetic nerve activation
Guilherme, Adilson L.; Pedersen, David J.; Henchey, Elizabeth; Henriques, Felipe S.; Danai, Laura V.; Shen, Yuefei; Yenilmez, Batuhan; Jung, Dae Young; Kim, Jason K.; Lodhi, Irfan J.; Semenkovich, Clay F.; and Czech, Michael P., "Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming" (2017). UMass Metabolic Network Publications. 120.
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