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Publication
The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis
through attenuation of hepatic lipogenesis.
Authors Wang GX, Zhao XY, Meng ZX, Kern M, Dietrich A, Chen Z, Cozacov Z, Zhou D,
Okunade AL, Su X, Li S, Blüher M, Lin JD
Submitted By Submitted Externally on 7/25/2018
Status Published
Journal Nature medicine
Year 2014
Date Published 12/1/2014
Volume : Pages 20 : 1436 - 1443
PubMed Reference 25401691
Abstract Brown fat activates uncoupled respiration in response to cold temperature and
contributes to systemic metabolic homeostasis. To date, the metabolic action of
brown fat has been primarily attributed to its role in fuel oxidation and
uncoupling protein 1 (UCP1)-mediated thermogenesis. Whether brown fat engages
other tissues through secreted factors remains largely unexplored. Here we show
that neuregulin 4 (Nrg4), a member of the epidermal growth factor (EGF) family
of extracellular ligands, is highly expressed in adipose tissues, enriched in
brown fat and markedly increased during brown adipocyte differentiation. Adipose
tissue Nrg4 expression was reduced in rodent and human obesity. Gain- and
loss-of-function studies in mice demonstrated that Nrg4 protects against
diet-induced insulin resistance and hepatic steatosis through attenuating
hepatic lipogenic signaling. Mechanistically, Nrg4 activates ErbB3 and ErbB4
signaling in hepatocytes and negatively regulates de novo lipogenesis mediated
by LXR and SREBP1c in a cell-autonomous manner. These results establish Nrg4 as
a brown fat-enriched endocrine factor with therapeutic potential for the
treatment of obesity-associated disorders, including type 2 diabetes and
nonalcoholic fatty liver disease (NAFLD).




Strains




Genes
SymbolDescription
Nrg4neuregulin 4

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