Increased hepatic FAT/CD36, PTP1B and decreased HNF4A expression contributes to dyslipidemia associated with ethanol-induced liver dysfunction: Rescue effect of ginger extract.

Abstract

The association between chronic alcohol consumption and the development of alcpholic liver disease is a very well known phenomenon, but the precise underlying molecular mediators involved in ethanol-induced liver disease remain elusive. This study aimed to characterize the lipid metabolism alterations and the molecular mediators which are related to lipid metabolism in liver under the heavy ethanol exposure alone or combined with ginger extract. Twenty-four male wistar rats were assigned into three groups, namely control, ethanol, and ginger extract treated ethanol (GETE) groups. Six weeks after the treatment, the ethanol group showed a significant increase in fatty acid translocase (FAT)/CD36, protein tyrosine phosphatase 1B (PTP1B) and decrease hepatocyte nuclear factor 4 Alpha (HNF4A) genes expressions compared to the control group. The ethanol administration also significantly increased plasma LDL, cholesterol, triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to the control group. Moreover, compared to the control group, the ethanol group showed liver histhological changes, such as fibrosis, focal microvesicular steatosis, some apoptotic hepatocytes, spotty necrosis, portal lymphocytic inflammation, mallory-denk bodies, giant mitochondria, piecemeal necrosis. Consumption of ginger extract along with ethanol, partially ameliorated gene expression alteration and histological changes, improved undesirable lipid profile and liver enzymes changes compare to those in the ethanol group. These findings indicate that ethanol-induced liver abnormalities may in part be associated with lipid homeostasis changes mediated by overexpression of FAT/CD36, PTP1B and downexpressionof HNF4A genes. It also show that these effects can be reduced by using ginger extract as an antioxidant and anti-inflammatory agent.

• Authors: Alireza Shirpoor, Elaheh Heshmati, Fatemeh Kheradmand, Farzaneh Hosseini Gharalari, Leila Chodari, Roya Naderi, Farideh Nezami Majd, Mahrokh Samadi
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 105 Pg. 144-150 (Sep 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 29852391 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• CD36 Antigens
• Hepatocyte Nuclear Factor 4
• Hnf4a protein, rat
• Plant Extracts
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Ptpn1 protein, rat

Topics

• Animals
• CD36 Antigens (genetics, metabolism)
• Dyslipidemias (complications, drug therapy, metabolism)
• Gene Expression (drug effects)
• Zingiber officinale (chemistry)
• Hepatocyte Nuclear Factor 4 (genetics, metabolism)
• Lipid Metabolism (drug effects)
• Liver (drug effects, immunology, metabolism)
• Liver Diseases, Alcoholic (complications, drug therapy, metabolism)
• Liver Function Tests
• Male
• Plant Extracts (isolation & purification, therapeutic use)
• Protein Tyrosine Phosphatase, Non-Receptor Type 1 (genetics, metabolism)
• Rats, Wistar