Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming

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 homeostasi...

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Main Authors: Adilson Guilherme (Author), David J. Pedersen (Author), Elizabeth Henchey (Author), Felipe S. Henriques (Author), Laura V. Danai (Author), Yuefei Shen (Author), Batuhan Yenilmez (Author), DaeYoung Jung (Author), Jason K. Kim (Author), Irfan J. Lodhi (Author), Clay F. Semenkovich (Author), Michael P. Czech (Author)
Format: Book
Published: Elsevier, 2017-08-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Adilson Guilherme  |e author 
700 1 0 |a David J. Pedersen  |e author 
700 1 0 |a Elizabeth Henchey  |e author 
700 1 0 |a Felipe S. Henriques  |e author 
700 1 0 |a Laura V. Danai  |e author 
700 1 0 |a Yuefei Shen  |e author 
700 1 0 |a Batuhan Yenilmez  |e author 
700 1 0 |a DaeYoung Jung  |e author 
700 1 0 |a Jason K. Kim  |e author 
700 1 0 |a Irfan J. Lodhi  |e author 
700 1 0 |a Clay F. Semenkovich  |e author 
700 1 0 |a Michael P. Czech  |e author 
245 0 0 |a Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming 
260 |b Elsevier,   |c 2017-08-01T00:00:00Z. 
500 |a 2212-8778 
500 |a 10.1016/j.molmet.2017.05.012 
520 |a 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 & 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. 
546 |a EN 
690 |a Adipocytes 
690 |a de novo lipogenesis 
690 |a iWAT browning 
690 |a Glucose homeostasis 
690 |a Sympathetic nerve activation 
690 |a Internal medicine 
690 |a RC31-1245 
655 7 |a article  |2 local 
786 0 |n Molecular Metabolism, Vol 6, Iss 8, Pp 781-796 (2017) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2212877817302867 
787 0 |n https://doaj.org/toc/2212-8778 
856 4 1 |u https://doaj.org/article/6bc9d2917df04eb3b86d55ef045f6e28  |z Connect to this object online.