Role of ghrelin hormone in the development of alcohol-associated liver disease
Fatty liver is the earliest response of the liver to excessive alcohol consumption. Previously we identified that chronic alcohol administration increases levels of stomach-derived hormone, ghrelin, which by reducing circulating insulin levels, ultimately contributes to the development of alcohol-as...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332224004797 |
| _version_ | 1797200905263644672 |
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| author | Sundararajan Mahalingam Ramesh Bellamkonda Kusum K. Kharbanda Madan Kumar Arumugam Vikas Kumar Carol A. Casey Lorenzo Leggio Karuna Rasineni |
| author_facet | Sundararajan Mahalingam Ramesh Bellamkonda Kusum K. Kharbanda Madan Kumar Arumugam Vikas Kumar Carol A. Casey Lorenzo Leggio Karuna Rasineni |
| author_sort | Sundararajan Mahalingam |
| collection | DOAJ |
| description | Fatty liver is the earliest response of the liver to excessive alcohol consumption. Previously we identified that chronic alcohol administration increases levels of stomach-derived hormone, ghrelin, which by reducing circulating insulin levels, ultimately contributes to the development of alcohol-associated liver disease (ALD). In addition, ghrelin directly promotes fat accumulation in hepatocytes by enhancing de novo lipogenesis. Other than promoting ALD, ghrelin is known to increase alcohol craving and intake. In this study, we used a ghrelin receptor (GHSR) knockout (KO) rat model to characterize the specific contribution of ghrelin in the development of ALD with emphasis on energy homeostasis. Male Wistar wild type (WT) and GHSR-KO rats were pair-fed the Lieber-DeCarli control or ethanol diet for 6 weeks. At the end of the feeding period, glucose tolerance test was conducted, and tissue samples were collected. We observed reduced alcohol intake by GHSR-KOs compared to a previous study where WT rats were fed ethanol diet ad libitum. Further, when the WTs were pair-fed to GHSR-KOs, the KO rats exhibited resistance to develop ALD through improving insulin secretion/sensitivity to reduce adipose lipolysis and hepatic fatty acid uptake/synthesis and increase fatty acid oxidation. Furthermore, proteomic data revealed that ethanol-fed KO exhibit less alcohol-induced mitochondrial dysfunction and oxidative stress than WT rats. Proteomic data also confirmed that the ethanol-fed KOs are insulin sensitive and are resistant to hepatic steatosis development compared to WT rats. Together, these data confirm that inhibiting ghrelin action prevent alcohol-induced liver and adipose dysfunction independent of reducing alcohol intake. |
| first_indexed | 2024-04-24T07:39:04Z |
| format | Article |
| id | doaj.art-b9357bba242e491aa09ac86d028401a4 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-24T07:39:04Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-b9357bba242e491aa09ac86d028401a42024-04-20T04:17:12ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-05-01174116595Role of ghrelin hormone in the development of alcohol-associated liver diseaseSundararajan Mahalingam0Ramesh Bellamkonda1Kusum K. Kharbanda2Madan Kumar Arumugam3Vikas Kumar4Carol A. Casey5Lorenzo Leggio6Karuna Rasineni7Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USAResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USAResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USAResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USAMass Spectrometry and Proteomic Core Facility, University of Nebraska Medical Center, Omaha, NE, USA; Department of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE, USAResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USAClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse, Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, Baltimore, MD, USA; Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA; Division of Addiction Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Department of Neuroscience, Georgetown University Medical Center, Washington DC, USAResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Corresponding author at: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Nebraska Medical Center, DRC1, R6050, Omaha, NE 68198-5870, USA.Fatty liver is the earliest response of the liver to excessive alcohol consumption. Previously we identified that chronic alcohol administration increases levels of stomach-derived hormone, ghrelin, which by reducing circulating insulin levels, ultimately contributes to the development of alcohol-associated liver disease (ALD). In addition, ghrelin directly promotes fat accumulation in hepatocytes by enhancing de novo lipogenesis. Other than promoting ALD, ghrelin is known to increase alcohol craving and intake. In this study, we used a ghrelin receptor (GHSR) knockout (KO) rat model to characterize the specific contribution of ghrelin in the development of ALD with emphasis on energy homeostasis. Male Wistar wild type (WT) and GHSR-KO rats were pair-fed the Lieber-DeCarli control or ethanol diet for 6 weeks. At the end of the feeding period, glucose tolerance test was conducted, and tissue samples were collected. We observed reduced alcohol intake by GHSR-KOs compared to a previous study where WT rats were fed ethanol diet ad libitum. Further, when the WTs were pair-fed to GHSR-KOs, the KO rats exhibited resistance to develop ALD through improving insulin secretion/sensitivity to reduce adipose lipolysis and hepatic fatty acid uptake/synthesis and increase fatty acid oxidation. Furthermore, proteomic data revealed that ethanol-fed KO exhibit less alcohol-induced mitochondrial dysfunction and oxidative stress than WT rats. Proteomic data also confirmed that the ethanol-fed KOs are insulin sensitive and are resistant to hepatic steatosis development compared to WT rats. Together, these data confirm that inhibiting ghrelin action prevent alcohol-induced liver and adipose dysfunction independent of reducing alcohol intake.http://www.sciencedirect.com/science/article/pii/S0753332224004797Chronic alcoholFatty liver diseaseOrgan crosstalkGhrelinGHSRGut peptides |
| spellingShingle | Sundararajan Mahalingam Ramesh Bellamkonda Kusum K. Kharbanda Madan Kumar Arumugam Vikas Kumar Carol A. Casey Lorenzo Leggio Karuna Rasineni Role of ghrelin hormone in the development of alcohol-associated liver disease Biomedicine & Pharmacotherapy Chronic alcohol Fatty liver disease Organ crosstalk Ghrelin GHSR Gut peptides |
| title | Role of ghrelin hormone in the development of alcohol-associated liver disease |
| title_full | Role of ghrelin hormone in the development of alcohol-associated liver disease |
| title_fullStr | Role of ghrelin hormone in the development of alcohol-associated liver disease |
| title_full_unstemmed | Role of ghrelin hormone in the development of alcohol-associated liver disease |
| title_short | Role of ghrelin hormone in the development of alcohol-associated liver disease |
| title_sort | role of ghrelin hormone in the development of alcohol associated liver disease |
| topic | Chronic alcohol Fatty liver disease Organ crosstalk Ghrelin GHSR Gut peptides |
| url | http://www.sciencedirect.com/science/article/pii/S0753332224004797 |
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