Gpnmb secreted from liver promotes lipogenesis in white adipose tissue and aggravates obesity and insulin resistance

Nature Metabolism
Xue-Min GongBao-Liang Song

Abstract

Metabolism in mammals is regulated by complex interplay among different organs. Fatty acid synthesis is increased in white adipose tissue (WAT) when it is inhibited in the liver. Here we identify glycoprotein non-metastatic melanoma protein B (Gpnmb) as one liver-WAT cross-talk factor involved in lipogenesis. Inhibition of the hepatic sterol regulatory element-binding protein pathway leads to increased transcription of Gpnmb and promotes processing of the membrane protein to a secreted form. Gpnmb stimulates lipogenesis in WAT and exacerbates diet-induced obesity and insulin resistance. In humans, Gpnmb is tightly associated with body mass index and is a strong risk factor for obesity. Gpnmb inhibition by a neutralizing antibody or liver-specific knockdown improves metabolic parameters, including weight gain reduction and increased insulin sensitivity, probably by promoting the beiging of WAT. These results suggest that Gpnmb is a liver-secreted factor regulating lipogenesis in WAT, and that Gpnmb inhibition may provide a therapeutic strategy in obesity and diabetes.

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Citations

May 24, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pei-Suen Tsou, Amr H Sawalha
May 1, 2019·Nature Metabolism·Henry Kuang, Jiandie D Lin
Sep 1, 2021·Neurobiology of Disease·Robert BrendzaBrad A Friedman
Oct 6, 2021·Scientific Reports·Bernadette NicklMichael Bader

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Methods Mentioned

BETA
ubiquitination
PCR
ELISA
immunoprecipitation
enzyme-linked immunosorbent assay
transfection
electrophoresis
Feature Extraction

Clinical Trials Mentioned

NCT01084967

Software Mentioned

GraphPad Prism
Gene Spring
Feature Extraction
SAS

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