Brown fat activation mitigates alcohol-induced liver steatosis and injury in mice
Hong Shen, … , M. Bishr Omary, Liangyou Rui
Hong Shen, … , M. Bishr Omary, Liangyou Rui
Published March 19, 2019
Citation Information: J Clin Invest. 2019;129(6):2305-2317. https://doi.org/10.1172/JCI124376.
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Research Article Hepatology Article has an altmetric score of 35

Brown fat activation mitigates alcohol-induced liver steatosis and injury in mice

Abstract

Chronic alcohol consumption causes liver injury, inflammation, and fibrosis, thereby increasing morbidity and mortality. Paradoxically, modest drinking is believed to confer metabolic improvement, but the underlying mechanism remains elusive. Here, we have identified a hepatoprotective brain/brown adipose tissue (BAT)/liver axis. Alcohol consumption or direct alcohol administration into the brain stimulated hypothalamic neural circuits and sympathetic nerves innervating BAT and dramatically increased BAT uncoupling protein 1 (Ucp1) expression and activity in a BAT-sympathetic nerve-dependent manner. BAT and beige fat oxidized fatty acids to fuel Ucp1-mediated thermogenesis, thereby inhibiting lipid trafficking into the liver. BAT also secreted several adipokines, including adiponectin, which suppressed hepatocyte injury and death. Genetic deletion of Ucp1 profoundly augmented alcohol-induced liver steatosis, injury, inflammation, and fibrosis in male and female mice. Conversely, activation of BAT and beige fat through cold exposure suppressed alcoholic liver disease development. Our results unravel an unrecognized brain alcohol-sensing/sympathetic nerve/BAT/liver axis that counteracts liver steatosis and injury.

Authors

Hong Shen, Lin Jiang, Jiandie D. Lin, M. Bishr Omary, Liangyou Rui

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