Chronic alcohol exposure alters circulating insulin and ghrelin levels: role of ghrelin in hepatic steatosis

Authors

Karuna Rasineni, University of Nebraska Medical CenterFollow
Paul G. Thomes, University of Nebraska Medical CenterFollow
Jacy L. Kubik, University of Nebraska Medical CenterFollow
Edward N. Harris, University of Nebraska - LincolnFollow
Kusum K. Kharbanda, University of Nebraska Medical CenterFollow
Carol A. Casey, University of Nebraska Medical CenterFollow

Document Type

Article

Date of this Version

2019

Citation

Am J Physiol Gastrointest Liver Physiol 316: G453–G461, 2019

Comments

This document is a U.S. government work and is not subject to copyright in the United States.

doi:10.1152/ajpgi.00334.2018

Abstract

Fatty liver is the earliest response of the liver to excessive ethanol consumption. Central in the development of alcoholic steatosis is increased mobilization of nonesterified free fatty acids (NEFAs) to the liver from the adipose tissue. In this study, we hypothesized that ethanol-induced increase in ghrelin by impairing insulin secretion, could be responsible for the altered lipid metabolism observed in adipose and liver tissue. Male Wistar rats were fed for 5–8 wk with control or ethanol Lieber-DeCarli diet, followed by biochemical analyses in serum and liver tissues. In addition, in vitro studies were conducted on pancreatic islets isolated from experimental rats. We found that ethanol increased serum ghrelin and decreased serum insulin levels in both fed and fasting conditions. These results were corroborated by our observations of a significant accumulation of insulin in pancreatic islets of ethanol-fed rats, indicating that its secretion was impaired. Furthermore, ethanol-induced reduction in circulating insulin was associated with lower adipose weight and increased NEFA levels observed in these rats. Additionally, we found that increased concentration of serum ghrelin was due to increased synthesis and maturation in the stomach of the ethanol-fed rats. We also report that in addition to its effect on the pancreas, ghrelin can also directly act on hepatocytes via the ghrelin receptors and promote fat accumulation. In conclusion, alcohol-induced elevation of circulating ghrelin levels impairs insulin secretion. Consequently, reduced circulating insulin levels likely contribute to increased free fatty acid mobilization from adipose tissue to liver, thereby contributing to hepatic steatosis.