Deregulation of hepatic lipid metabolism associated with insulin resistance in rats subjected to chronic monocrotophos exposure

2020 ◽  
Vol 34 (8) ◽  
Author(s):  
Raju Nagaraju ◽  
Apurva K. R. Joshi ◽  
Sowmya G. Vamadeva ◽  
Padmanabhan S. Rajini
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

scholarly journals Herbal Formula HT048 Attenuates Diet-Induced Obesity by Improving Hepatic Lipid Metabolism and Insulin Resistance in Obese Rats

Molecules ◽  
2016 ◽  
Vol 21 (11) ◽  
pp. 1424 ◽  
Author(s):  
Yoon Lee ◽  
Bora Jin ◽  
Sung Lee ◽  
MiKyung Song ◽  
HyeonHui Bae ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Herbal Formula ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Diet Induced Obesity ◽  
Obese Rats

scholarly journals Liver-specific ceramide reduction alleviates steatosis and insulin resistance in alcohol-fed mice

2020 ◽  
Vol 61 (7) ◽  
pp. 983-994 ◽  
Author(s):  
Jason Correnti ◽  
Chelsea Lin ◽  
Jascha Brettschneider ◽  
Amy Kuriakose ◽  
Sookyoung Jeon ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Energy Homeostasis ◽  
Acid Ceramidase ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Stress Markers ◽  
Hepatic Insulin Signaling ◽  
Initial Stage ◽  
Target Effects

Alcohol’s impairment of both hepatic lipid metabolism and insulin resistance (IR) are key drivers of alcoholic steatosis, the initial stage of alcoholic liver disease (ALD). Pharmacologic reduction of lipotoxic ceramide prevents alcoholic steatosis and glucose intolerance in mice, but potential off-target effects limit its strategic utility. Here, we employed a hepatic-specific acid ceramidase (ASAH) overexpression model to reduce hepatic ceramides in a Lieber-DeCarli model of experimental alcoholic steatosis. We examined effects of alcohol on hepatic lipid metabolism, body composition, energy homeostasis, and insulin sensitivity as measured by hyperinsulinemic-euglycemic clamp. Our results demonstrate that hepatic ceramide reduction ameliorates the effects of alcohol on hepatic lipid droplet (LD) accumulation by promoting VLDL secretion and lipophagy, the latter of which involves ceramide cross-talk between the lysosomal and LD compartments. We additionally demonstrate that hepatic ceramide reduction prevents alcohol’s inhibition of hepatic insulin signaling. These effects on the liver are associated with a reduction in oxidative stress markers and are relevant to humans, as we observe peri- LD ASAH expression in human ALD. Together, our results suggest a potential role for hepatic ceramide inhibition in preventing ALD.

scholarly journals ULK1 Regulates Hepatic Lipid Metabolism via Autophagy Independent Mechanisms

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A303-A303
Author(s):  
Young Do Koo ◽  
Romilia Tatiana Castillo ◽  
Antentor Othrell Hinton ◽  
Evan Dale Abel
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Chow Diet ◽  
Hepatic Lipid Metabolism ◽  
Critical Pathway ◽  
Hepatic Lipid ◽  
Normal Chow

Abstract Non-alcoholic steatohepatitis (NASH), a major complication of obesity, diabetes, and metabolic syndrome has emerged as a leading cause of chronic liver disease and a risk factor for hepatocellular carcinoma. Autophagy is a critical pathway for the degradation of intracellular components by lysosomes. Established functions for autophagy in hepatic lipid metabolism and insulin sensitivity suggest a mechanistic link between altered autophagy and NASH. However, the interactions between insulin sensitivity, NASH, and autophagy are incompletely understood. The Unc-51 Like Autophagy Activating Kinase 1 (ULK1) is the only serine/threonine kinase in the core autophagy pathway and thus represents an excellent drug target. In this study, we observed that ULK1 may directly regulate insulin signaling and lipid metabolism via mechanisms that might involve modulation of AKT dephosphorylation. Surprisingly, silencing ULK1 did not significantly alter autophagy in hepatocytes despite impairing insulin-stimulated activation of AKT. To further elucidate the autophagy-independent role of ULK1 in hepatic lipid metabolism and insulin action, ULK1 liver-specific knock-out mice were generated. L-ULK1 KO mice exhibited impaired glucose tolerance and insulin resistance on a normal chow diet or 60% high-fat diet (HFD). In young mice (4 weeks after birth), the expression of genes that regulate de novo lipogenesis, such as FAS, SCD1, and SREBP1-c were induced in livers of L-ULK1KO mice even prior to the development of insulin resistance and obesity. Hepatomegaly and lipid accumulation developed in L-ULK1KO on normal chow and was exacerbated relative to wild type mice on a HFD. Serum concentrations of insulin, triglyceride, cholesterol, AST and ALT were significantly increased. In contrast, L-ULK2 KO mice were phenotypically normal. To identify putative novel ULK1 targets, we conducted a phospho-proteomics screen in a ULK1 deficient hepatocyte cell line. We identified a relatively small number of novel proteins whose phosphorylation levels were reduced by ULK1 deficiency. The identification of these targets supports autophagy-independent mechanisms of action of ULK1. Recently, we confirmed that NCOA3, one of the targets regulates hepatic lipid metabolism by interacting directly with ULK1. These data suggest that ULK-1 may regulate cellular targets that regulate hepatic lipid metabolism and insulin sensitivity.

Altered hepatic lipid metabolism in leptin-deficlent mice

2001 ◽  
Vol 120 (5) ◽  
pp. A546-A546
Author(s):  
D SWARTZBASILE ◽  
M GOLDBLATT ◽  
C SVATEK ◽  
M WALTERS ◽  
S CHOI ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

Prenatal programming of hepatic lipid metabolism: Sex, hormones and lifelong health

2020 ◽  
Author(s):  
Katarzyna Siemienowicz ◽  
Panagiotis Filis ◽  
Chiara Talia ◽  
Jennifer Thomas ◽  
Paul Fowler ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Sex Hormones ◽  
Prenatal Programming ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid
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