Neuronal modulation of hepatic lipid accumulation induced by bingelike drinking

Author:

Ibars Maria1,Maier Matthew T.1,Yulyaningsih Ernie1,Perez Luz1,Cheang Rachel1,Vilhelmsson Anna1,Louie Sharon M.2,Wegner Scott A.3,Yuan Xiaoyi4,Eltzschig Holger K.4,Hopf Frederic W.3,Nomura Daniel K.2,Koliwad Suneil K.15,Xu Allison W.16

Affiliation:

1. Diabetes Center, Department of Anatomy, University of California, San Francisco, California

2. Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology, University of California, Berkeley, California

3. Department of Neurology, Department of Anatomy, University of California, San Francisco, California

4. Department of Anesthesiology, University of Texas Health Science Center at Houston, Houston, Texas

5. Department of Medicine, Department of Anatomy, University of California, San Francisco, California

6. Department of Anatomy, University of California, San Francisco, California

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 A2Bsignaling 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.

Funder

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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