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Ghrelin regulates adipose tissue metabolism: Role in hepatic steatosis.
Chem Biol Interact. 2020 May 01; 322:109059.CB

Abstract

Fatty liver is the earliest and most common response of the liver to consumption of excessive alcohol. Steatosis can predispose the fatty liver to develop progressive liver damage. Chief among the many mechanisms involved in development of hepatic steatosis is dysregulation of insulin-mediated adipose tissue metabolism. Particularly, it is the enhanced adipose lipolysis-derived free fatty acids and their delivery to the liver that ultimately results in hepatic steatosis. The adipose-liver axis is modulated by hormones, particularly insulin and adiponectin. In recent studies, we demonstrated that an alcohol-induced increase in serum ghrelin levels impairs insulin secretion from pancreatic β-cells. The consequent reduction in circulating insulin levels promotes adipose lipolysis and mobilization of fatty acids to the liver to ultimately contribute to hepatic steatosis. Because many tissues, including adipose tissue, express ghrelin receptor we hypothesized that ghrelin may directly affect energy metabolism in adipocytes. We have exciting new preliminary data which shows that treatment of premature 3T3-L1 adipocytes with ghrelin impairs adipocyte differentiation and inhibits lipid accumulation in the tissue designed to store energy in the form of fat. We further observed that ghrelin treatment of differentiated adipocytes significantly inhibited secretion of adiponectin, a hepatoprotective hormone that reduces lipid synthesis and promotes lipid oxidation. These results were corroborated by our observations of a significant increase in serum adiponectin levels in ethanol-fed rats treated with a ghrelin receptor antagonist verses the un-treated ethanol-fed rats. Interestingly, in adipocytes, ghrelin also increases secretion of interleukin-6 (IL-6) and CCL2 (chemokine [C-C motif] ligand 2), cytokines which promote hepatic inflammation and progression of liver disease. To summarize, the alcohol-induced increase in serum ghrelin levels dysregulates adipose-liver interaction and promotes hepatic steatosis by increasing the free fatty acid released from adipose for hepatic uptake, and by altering adiponectin and cytokine secretion. Taken together, our data indicates that targeting the activity of ghrelin may be a powerful treatment strategy.

Authors+Show Affiliations

Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Research Service, Veterans' Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, USA. Electronic address: Karuna.rasineni@unmc.edu.Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Research Service, Veterans' Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, USA.Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Research Service, Veterans' Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, USA.Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, USA.Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Research Service, Veterans' Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Research Service, Veterans' Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32171850

Citation

Rasineni, Karuna, et al. "Ghrelin Regulates Adipose Tissue Metabolism: Role in Hepatic Steatosis." Chemico-biological Interactions, vol. 322, 2020, p. 109059.
Rasineni K, Kubik JL, Knight KL, et al. Ghrelin regulates adipose tissue metabolism: Role in hepatic steatosis. Chem Biol Interact. 2020;322:109059.
Rasineni, K., Kubik, J. L., Knight, K. L., Hall, L., Casey, C. A., & Kharbanda, K. K. (2020). Ghrelin regulates adipose tissue metabolism: Role in hepatic steatosis. Chemico-biological Interactions, 322, 109059. https://doi.org/10.1016/j.cbi.2020.109059
Rasineni K, et al. Ghrelin Regulates Adipose Tissue Metabolism: Role in Hepatic Steatosis. Chem Biol Interact. 2020 May 1;322:109059. PubMed PMID: 32171850.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ghrelin regulates adipose tissue metabolism: Role in hepatic steatosis. AU - Rasineni,Karuna, AU - Kubik,Jacy L, AU - Knight,Kurt L, AU - Hall,Lukas, AU - Casey,Carol A, AU - Kharbanda,Kusum K, Y1 - 2020/03/11/ PY - 2019/10/26/received PY - 2020/03/10/accepted PY - 2020/3/17/pubmed PY - 2020/4/14/medline PY - 2020/3/16/entrez KW - Adipose tissue KW - Alcoholic fatty liver KW - Ghrelin SP - 109059 EP - 109059 JF - Chemico-biological interactions JO - Chem. Biol. Interact. VL - 322 N2 - Fatty liver is the earliest and most common response of the liver to consumption of excessive alcohol. Steatosis can predispose the fatty liver to develop progressive liver damage. Chief among the many mechanisms involved in development of hepatic steatosis is dysregulation of insulin-mediated adipose tissue metabolism. Particularly, it is the enhanced adipose lipolysis-derived free fatty acids and their delivery to the liver that ultimately results in hepatic steatosis. The adipose-liver axis is modulated by hormones, particularly insulin and adiponectin. In recent studies, we demonstrated that an alcohol-induced increase in serum ghrelin levels impairs insulin secretion from pancreatic β-cells. The consequent reduction in circulating insulin levels promotes adipose lipolysis and mobilization of fatty acids to the liver to ultimately contribute to hepatic steatosis. Because many tissues, including adipose tissue, express ghrelin receptor we hypothesized that ghrelin may directly affect energy metabolism in adipocytes. We have exciting new preliminary data which shows that treatment of premature 3T3-L1 adipocytes with ghrelin impairs adipocyte differentiation and inhibits lipid accumulation in the tissue designed to store energy in the form of fat. We further observed that ghrelin treatment of differentiated adipocytes significantly inhibited secretion of adiponectin, a hepatoprotective hormone that reduces lipid synthesis and promotes lipid oxidation. These results were corroborated by our observations of a significant increase in serum adiponectin levels in ethanol-fed rats treated with a ghrelin receptor antagonist verses the un-treated ethanol-fed rats. Interestingly, in adipocytes, ghrelin also increases secretion of interleukin-6 (IL-6) and CCL2 (chemokine [C-C motif] ligand 2), cytokines which promote hepatic inflammation and progression of liver disease. To summarize, the alcohol-induced increase in serum ghrelin levels dysregulates adipose-liver interaction and promotes hepatic steatosis by increasing the free fatty acid released from adipose for hepatic uptake, and by altering adiponectin and cytokine secretion. Taken together, our data indicates that targeting the activity of ghrelin may be a powerful treatment strategy. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/32171850/Ghrelin_regulates_adipose_tissue_metabolism:_Role_in_hepatic_steatosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(19)31794-6 DB - PRIME DP - Unbound Medicine ER -