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Open AccessFeature PaperArticle

Inhibition of Ghrelin Activity by Receptor Antagonist [d-Lys-3] GHRP-6 Attenuates Alcohol-Induced Hepatic Steatosis by Regulating Hepatic Lipid Metabolism

by 1,2,*, 1,2, 1,2,† and 1,2,†
1
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
2
Research Service, Veterans’ Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2019, 9(10), 517; https://doi.org/10.3390/biom9100517
Received: 4 September 2019 / Revised: 18 September 2019 / Accepted: 19 September 2019 / Published: 21 September 2019
(This article belongs to the Collection Multi-Organ Alcohol-Related Damage: Mechanisms and Treatment)
Alcoholic steatosis, characterized by an accumulation of triglycerides in hepatocytes, is one of the earliest pathological changes in the progression of alcoholic liver disease. In our previous study, we showed that alcohol-induced increase in serum ghrelin levels impair insulin secretion from pancreatic β-cells. The consequent reduction in the circulating insulin levels promote adipose-derived fatty acid mobilization to ultimately contribute to hepatic steatosis. In this study, we determined whether inhibition of ghrelin activity in chronic alcohol-fed rats could improve hepatic lipid homeostasis at the pancreas–adipose–liver axis. Adult Wistar rats were fed Lieber-DeCarli control or an ethanol liquid diet for 7 weeks. At 6 weeks, a subset of rats in each group were injected with either saline or ghrelin receptor antagonist, [d-Lys-3] GHRP-6 (DLys; 9 mg/kg body weight) for 5 days and all rats were sacrificed 2 days later. DLys treatment of ethanol rats improved pancreatic insulin secretion, normalized serum insulin levels, and the adipose lipid metabolism, as evidenced by the decreased serum free fatty acids (FFA). DLys treatment of ethanol rats also significantly decreased the circulating FFA uptake, de novo hepatic fatty acid synthesis ultimately attenuating alcoholic steatosis. To summarize, inhibition of ghrelin activity reduced alcoholic steatosis by improving insulin secretion, normalizing serum insulin levels, inhibiting adipose lipolysis, and preventing fatty acid uptake and synthesis in the liver. Our studies provided new insights on the important role of ghrelin in modulating the pancreas–adipose–liver, and promoting adipocyte lipolysis and hepatic steatosis. The findings offer a therapeutic approach of not only preventing alcoholic liver injury but also treating it. View Full-Text
Keywords: alcoholic fatty liver; insulin; ghrelin; adipose tissue; [d-Lys-3] GHRP-6 alcoholic fatty liver; insulin; ghrelin; adipose tissue; [d-Lys-3] GHRP-6
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MDPI and ACS Style

Rasineni, K.; Kubik, J.L.; Casey, C.A.; Kharbanda, K.K. Inhibition of Ghrelin Activity by Receptor Antagonist [d-Lys-3] GHRP-6 Attenuates Alcohol-Induced Hepatic Steatosis by Regulating Hepatic Lipid Metabolism. Biomolecules 2019, 9, 517. https://doi.org/10.3390/biom9100517

AMA Style

Rasineni K, Kubik JL, Casey CA, Kharbanda KK. Inhibition of Ghrelin Activity by Receptor Antagonist [d-Lys-3] GHRP-6 Attenuates Alcohol-Induced Hepatic Steatosis by Regulating Hepatic Lipid Metabolism. Biomolecules. 2019; 9(10):517. https://doi.org/10.3390/biom9100517

Chicago/Turabian Style

Rasineni, Karuna; Kubik, Jacy L.; Casey, Carol A.; Kharbanda, Kusum K. 2019. "Inhibition of Ghrelin Activity by Receptor Antagonist [d-Lys-3] GHRP-6 Attenuates Alcohol-Induced Hepatic Steatosis by Regulating Hepatic Lipid Metabolism" Biomolecules 9, no. 10: 517. https://doi.org/10.3390/biom9100517

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