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Publication
Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate
diet-induced metabolic disorders.
Authors Chen Z, Wang GX, Ma SL, Jung DY, Ha H, Altamimi T, Zhao XY, Guo L, Zhang P, Hu
CR, Cheng JX, Lopaschuk GD, Kim JK, Lin JD
Submitted By Submitted Externally on 8/17/2017
Status Published
Journal Molecular metabolism
Year 2017
Date Published
Volume : Pages 6 : 863 - 872
PubMed Reference 28752050
Abstract Brown and white adipose tissue exerts pleiotropic effects on systemic energy
metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was
recently identified as a brown fat-enriched secreted factor that ameliorates
diet-induced metabolic disorders, including insulin resistance and hepatic
steatosis. However, the physiological mechanisms through which Nrg4 regulates
energy balance and glucose and lipid metabolism remain incompletely understood.
The aims of the current study were: i) to investigate the regulation of adipose
Nrg4 expression during obesity and the physiological signals involved, ii) to
elucidate the mechanisms underlying Nrg4 regulation of energy balance and
glucose and lipid metabolism, and iii) to explore whether Nrg4 regulates adipose
tissue secretome gene expression and adipokine secretion., We examined the
correlation of adipose Nrg4 expression with obesity in a cohort of diet-induced
obese mice and investigated the upstream signals that regulate Nrg4 expression.
We performed metabolic cage and hyperinsulinemic-euglycemic clamp studies in
Nrg4 transgenic mice to dissect the metabolic pathways regulated by Nrg4. We
investigated how Nrg4 regulates hepatic lipid metabolism in the fasting state
and explored the effects of Nrg4 on adipose tissue gene expression, particularly
those encoding secreted factors., Adipose Nrg4 expression is inversely
correlated with adiposity and regulated by pro-inflammatory and
anti-inflammatory signaling. Transgenic expression of Nrg4 increases energy
expenditure and augments whole body glucose metabolism. Nrg4 protects mice from
diet-induced hepatic steatosis in part through activation of hepatic fatty acid
oxidation and ketogenesis. Finally, Nrg4 promotes a healthy adipokine profile
during obesity., Nrg4 exerts pleiotropic beneficial effects on energy balance
and glucose and lipid metabolism to ameliorate obesity-associated metabolic
disorders. Biologic therapeutics based on Nrg4 may improve both type 2 diabetes
and non-alcoholic fatty liver disease (NAFLD) in patients.






Genes
SymbolDescription
Nrg4neuregulin 4

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