Elsevier

Molecular Metabolism

Volume 6, Issue 8, August 2017, Pages 781-796
Molecular Metabolism

Original Article
Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming

https://doi.org/10.1016/j.molmet.2017.05.012Get rights and content
Under a Creative Commons license
open access

Highlights

  • Inducible deletion of FASN in white adipocytes of mature mice enhances browning of iWAT.

  • Inducible deletion of white adipocyte FASN in mature obese mice improves glucose tolerance.

  • Loss of FASN in white adipocytes enhances sympathetic nerve outflow in iWAT.

  • Crosstalk between adipocyte fat metabolism and neuronal stimulation of adipose tissue is proposed.

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.

Keywords

Adipocytes
de novo lipogenesis
iWAT browning
Glucose homeostasis
Sympathetic nerve activation

Cited by (0)

5

These authors contributed equally to this work.

6

Current address: Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.