Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming
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Authors
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.
Czech, Michael P.
UMass Chan Affiliations
UMass Metabolic NetworkDepartment of Medicine, Division of Endocrinology, Metabolism, and Diabetes
Program in Molecular Medicine
Document Type
Journal ArticlePublication Date
2017-05-31Keywords
Adipocytesde novo lipogenesis
iWAT browning
Glucose homeostasis
ssympathetic nerve activation
Biochemistry
Cell Biology
Cellular and Molecular Physiology
Molecular Biology
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Show full item recordAbstract
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.Source
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 siteDOI
10.1016/j.molmet.2017.05.012Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36601PubMed ID
28752043Related Resources
Link to Article in PubMedRights
Copyright © 2017 The Authors.Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.molmet.2017.05.012