UMMS Affiliation

Program in Molecular Medicine; Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes; UMass Metabolic Network

Publication Date


Document Type



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.


Adipocytes, de novo lipogenesis, iWAT browning, Glucose homeostasis, ssympathetic nerve activation

Rights and Permissions

Copyright © 2017 The Authors.

DOI of Published Version



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

Journal/Book/Conference Title

Molecular metabolism

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.