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

H Shen, L Jiang, JD Lin, MB Omary… - The Journal of Clinical …, 2019 - Am Soc Clin Investig
H Shen, L Jiang, JD Lin, MB Omary, L Rui
The Journal of Clinical Investigation, 2019Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation