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

2019 ◽  
Vol 316 (4) ◽  
pp. G453-G461 ◽  
Author(s):  
Karuna Rasineni ◽  
Paul G. Thomes ◽  
Jacy L. Kubik ◽  
Edward N. Harris ◽  
Kusum K. Kharbanda ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Secretion ◽  
Lipid Metabolism ◽  
Fatty Liver ◽  
Pancreatic Islets ◽  
Hepatic Steatosis ◽  
Liver Tissue ◽  
Serum Ghrelin ◽  
Altered Lipid Metabolism ◽  
Altered Lipid

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. NEW & NOTEWORTHY Our studies are the first to report that ethanol-induced increases in ghrelin contribute to impaired insulin secretion, which results in the altered lipid metabolism observed in adipose and liver tissue in the setting of alcoholic fatty liver disease.

scholarly journals Lysophosphatidylcholine acyltransferase 1 is downregulated by hepatitis C virus: impact on production of lipo-viro-particles

Gut ◽  
2016 ◽  
Vol 66 (12) ◽  
pp. 2160-2169 ◽  
Author(s):  
Frauke Beilstein ◽  
Matthieu Lemasson ◽  
Véronique Pène ◽  
Dominique Rainteau ◽  
Sylvie Demignot ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Liver Lipid ◽  
Very Low Density Lipoproteins ◽  
Viral Particles ◽  
Triacylglycerol Content ◽  
Liver Lipid Metabolism ◽  
Infectious Cycle ◽  
Altered Lipid Metabolism ◽  
Altered Lipid

ObjectiveHCV is intimately linked with the liver lipid metabolism, devoted to the efflux of triacylglycerols stored in lipid droplets (LDs) in the form of triacylglycerol-rich very-low-density lipoproteins (VLDLs): (i) the most infectious HCV particles are those of lowest density due to association with triacylglycerol-rich lipoproteins and (ii) HCV-infected patients frequently develop hepatic steatosis (increased triacylglycerol storage). The recent identification of lysophosphatidylcholine acyltransferase 1 (LPCAT1) as an LD phospholipid-remodelling enzyme prompted us to investigate its role in liver lipid metabolism and HCV infectious cycle.DesignHuh-7.5.1 cells and primary human hepatocytes (PHHs) were infected with JFH1-HCV. LPCAT1 depletion was achieved by RNA interference. Cells were monitored for LPCAT1 expression, lipid metabolism and HCV production and infectivity. The density of viral particles was assessed by isopycnic ultracentrifugation.ResultsUpon HCV infection, both Huh-7.5.1 cells and PHH had decreased levels of LPCAT1 transcript and protein, consistent with transcriptional downregulation. LPCAT1 depletion in either naive or infected Huh-7.5.1 cells resulted in altered lipid metabolism characterised by LD remodelling, increased triacylglycerol storage and increased secretion of VLDL. In infected Huh-7.5.1 cells or PHH, LPCAT1 depletion increased production of the viral particles of lowest density and highest infectivity.ConclusionsWe have identified LPCAT1 as a modulator of liver lipid metabolism downregulated by HCV, which appears as a viral strategy to increase the triacylglycerol content and hence infectivity of viral particles. Targeting this metabolic pathway may represent an attractive therapeutic approach to reduce both the viral titre and hepatic steatosis.

scholarly journals Transcription profiling in the liver of undernourished male rat offspring reveals altered lipid metabolism pathways and predisposition to hepatic steatosis

2019 ◽  
Vol 317 (6) ◽  
pp. E1094-E1107 ◽  
Author(s):  
Simon Lecoutre ◽  
Valérie Montel ◽  
Emmanuelle Vallez ◽  
Charlène Pourpe ◽  
Anne Delmont ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Fatty Liver ◽  
Cholesterol Metabolism ◽  
Saturated Fatty Acids ◽  
Male Rat ◽  
Chow Diet ◽  
Nonalcoholic Fatty Liver ◽  
Maternal Undernutrition ◽  
Altered Lipid Metabolism ◽  
Altered Lipid

Clinical and animal studies have reported an association between low birth weight and the development of nonalcoholic fatty liver disease (NAFLD) in offspring. Using a model of prenatal maternal 70% food restriction diet (FR30) in the rat, we previously showed that maternal undernutrition predisposes offspring to altered lipid metabolism in adipose tissue, especially on a high-fat (HF) diet. Here, using microarray-based expression profiling combined with metabolic, endocrine, biochemical, histological, and lipidomic approaches, we assessed whether FR30 procedure sensitizes adult male offspring to impaired lipid metabolism in the liver. No obvious differences were noted in the concentrations of triglycerides, cholesterol, and bile acids in the liver of 4-mo-old FR30 rats whichever postweaning diet was used. However, several clues suggest that offspring’s lipid metabolism and steatosis are modified by maternal undernutrition. First, lipid composition was changed (i.e., higher total saturated fatty acids and lower elaidic acid) in the liver, whereas larger triglyceride droplets were observed in hepatocytes of undernourished rats. Second, FR30 offspring exhibited long-term impact on hepatic gene expression and lipid metabolism pathways on a chow diet. Although the transcriptome profile was globally modified by maternal undernutrition, cholesterol and bile acid biosynthesis pathways appear to be key targets, indicating that FR30 animals were predisposed to impaired hepatic cholesterol metabolism. Third, the FR30 protocol markedly modifies hepatic gene transcription profiles in undernourished offspring in response to postweaning HF. Overall, FR30 offspring may exhibit impaired metabolic flexibility, which does not enable them to properly cope with postweaning nutritional challenges influencing the development of nonalcoholic fatty liver.

scholarly journals Integrated metabolomics reveals altered lipid metabolism in adipose tissue in a model of extreme longevity

GeroScience ◽  
2020 ◽  
Vol 42 (6) ◽  
pp. 1527-1546 ◽  
Author(s):  
Justin Darcy ◽  
Yimin Fang ◽  
Samuel McFadden ◽  
Matthew D. Lynes ◽  
Luiz O. Leiria ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Extreme Longevity ◽  
Altered Lipid Metabolism ◽  
Altered Lipid ◽  
Integrated Metabolomics

Integrated Metabolomics and Transcriptomics Analyses Reveal Altered Lipid Metabolism in Mouse Placentas Exposed to Alcohol

Placenta ◽  
2021 ◽  
Vol 112 ◽  
pp. e33
Author(s):  
Sze Ting (Cecilia) Kwan ◽  
Manjot Virdee ◽  
Nipun Saini ◽  
Kaylee Helfrich ◽  
Susan Smith
Keyword(s):  
Lipid Metabolism ◽  
Altered Lipid Metabolism ◽  
Altered Lipid ◽  
Integrated Metabolomics

The Decline of the Immune Response during Aging: the Role of an Altered Lipid Metabolism

1991 ◽  
Vol 621 (1 Physiological) ◽  
pp. 277-290 ◽  
Author(s):  
GEORG WICK ◽  
LUKAS A. HUBER ◽  
XU QING-BO ◽  
ELMAR JAROSCH ◽  
DIETHER SCHÖNITZER ◽  
...  
Keyword(s):  
Immune Response ◽  
Lipid Metabolism ◽  
Altered Lipid Metabolism ◽  
Altered Lipid

scholarly journals Systemic Overexpression of GDF5 in Adipocytes but Not Hepatocytes Alleviates High-Fat Diet-Induced Nonalcoholic Fatty Liver in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yan Yang ◽  
Wenting Zhang ◽  
Xiaohui Wu ◽  
Jing Wu ◽  
Chengjun Sun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Lentiviral Vector ◽  
Cell Model ◽  
Control Group ◽  
High Fat ◽  
Fatty Acid Binding ◽  
Nonalcoholic Fatty Liver

Objective. Our recent study demonstrated that growth differentiation factor 5 (GDF5) could promote white adipose tissue thermogenesis and alleviate high-fat diet- (HFD-) induced obesity in fatty acid-binding protein 4- (Fabp4-) GDF5 transgenic mice (TG). Here, we further investigated the effects of systemic overexpression of the GDF5 gene in adipocytes HFD-induced nonalcoholic fatty liver disease (NAFLD). Methods. Fabp4-GDF5 TG mice were administered an HFD feeding. NAFLD-related indicators associated with lipid metabolism and inflammation were measured. A GDF5 lentiviral vector was constructed, and the LO2 NAFLD cell model was induced by FFA solution (oleic acid and palmitic acid). The alterations in liver function, liver lipid metabolism, and related inflammatory indicators were analyzed. Results. The liver weight was significantly reduced in the TG group, which was in accordance with the significantly downregulated expression of TNFα, MCP1, Aim2, and SREBP-1c and significantly upregulated expression of CPT-1α and ACOX2 in TG mouse livers. Compared to that of cells in the FAA-free control group, LO2 cells with in situ overexpression of GDF5 developed lipid droplets after FFA treatment; the levels of triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly increased in both the GDF5 lentivirus and control lentivirus groups compared with those of the FAA-free group. Additionally, the levels of FAS, SREBP-1, CPT-1α, and inflammation-associated genes, such as ASC and NLRC4, were unaltered despite GDF5 treatment. Conclusion. Systemic overexpression of GDF5 in adipose tissue in vivo significantly reduced HFD-induced NAFLD liver damage in mice. The overexpression of GDF5 in hepatocytes failed to improve lipid accumulation and inflammation-related reactions induced by mixed fatty acids, suggesting that the protective effect of GDF5 in NAFLD was mainly due to the reduction in adipose tissue and improvements in metabolism. Hence, our study suggests that the management of NAFLD should be targeted to reduce the overall amount of body fat and improve metabolic status before the progression to nonalcoholic steatohepatitis occurs.

Sign in / Sign up

Export Citation Format

Share Document