Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming

Adilson Guilherme, David J. Pedersen, Elizabeth Henchey, Felipe S. Henriques, Laura V. Danai, Yuefei Shen, Batuhan Yenilmez, Dae Young Jung, Jason K. Kim, Irfan J. Lodhi, Clay F. Semenkovich, Michael P. Czech

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)781-796
Number of pages16
JournalMolecular Metabolism
Volume6
Issue number8
DOIs
StatePublished - Aug 2017

Keywords

  • Adipocytes
  • Glucose homeostasis
  • Sympathetic nerve activation
  • de novo lipogenesis
  • iWAT browning

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