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Publication
Neuronal modulation of hepatic lipid accumulation induced by bingelike drinking.
Authors Ibars M, Maier MT, Yulyaningsih E, Perez L, Cheang R, Vilhelmsson A, Louie SM,
Wegner SA, Yuan X, Eltzschig HK, Hopf FW, Nomura DK, Koliwad SK, Xu AW
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2020
Date Published 5/1/2020
Volume : Pages 318 : E655 - E666
PubMed Reference 32045262
Abstract Excessive alcohol consumption, including binge drinking, is a common cause of
fatty liver disease. Binge drinking rapidly induces hepatic steatosis, an early
step in the pathogenesis of chronic liver injury. Despite its prevalence, the
process by which excessive alcohol consumption promotes hepatic lipid
accumulation remains unclear. Alcohol exerts potent effects on the brain,
including hypothalamic neurons crucial for metabolic regulation. However,
whether or not the brain plays a role in alcohol-induced hepatic steatosis is
unknown. In the brain, alcohol increases extracellular levels of adenosine, a
potent neuromodulator, and previous work implicates adenosine signaling as being
important for the development of alcoholic fatty liver disease. Acute alcohol
exposure also increases both the activity of agouti-related protein
(AgRP)-expressing neurons and AgRP immunoreactivity. Here, we show that
adenosine receptor A2B signaling in the brain modulates the extent of
alcohol-induced fatty liver in mice and that both the AgRP neuropeptide and the
sympathetic nervous system are indispensable for hepatic steatosis induced by
bingelike alcohol consumption. Together, these results indicate that the brain
plays an integral role in alcohol-induced hepatic lipid accumulation and that
central adenosine signaling, hypothalamic AgRP, and the sympathetic nervous
system are crucial mediators of this process.




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