scholarly journals Hepatocyte-specific Expression of Human Carboxylesterase 2 Attenuates Non-alcoholic Steatohepatitis in Mice

2020 ◽  
Author(s):  
Yanyong Xu ◽  
Xiaoli Pan ◽  
Shuwei Hu ◽  
Yingdong Zhu ◽  
Fathima Cassim Bawa ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Regulatory Element ◽  
Acid Oxidation ◽  
Specific Expression ◽  
Alcoholic Fatty Liver ◽  
Triacylglycerol Hydrolase ◽  
High Fructose ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Apoptosis And Inflammation

Human carboxylesterase 2 (CES2) has triacylglycerol hydrolase (TGH) activities and plays an important role in lipolysis. In this study, we aim to determine the role of human CES2 in the progression or reversal of steatohepatitis in diet-induced or genetically obese mice. High-fat/high-cholesterol/high-fructose (HFCF) diet-fed C57BL/6 mice or db/db mice were i.v. injected with an adeno-associated virus expressing human CES2 under the control of an albumin promoter. Human CES2 protected against HFCF diet-induced non-alcoholic fatty liver disease (NAFLD) in C57BL/6J mice and reversed steatohepatitis in db/db mice. Human CES2 also improved glucose tolerance and insulin sensitivity. Mechanistically, human CES2 reduced hepatic triglyceride and free fatty acid levels by inducing lipolysis and fatty acid oxidation and inhibiting lipogenesis via suppression of sterol regulatory element-binding protein 1. Furthermore, human CES2 overexpression improved mitochondrial respiration and glycolytic function, and inhibited gluconeogenesis, lipid peroxidation, apoptosis and inflammation. Our data suggest that hepatocyte-specific expression of human CES2 prevents and reverses steatohepatitis. Targeting hepatic CES2 may be an attractive strategy for treatment of NAFLD.

Chronic exercise provides renal-protective effects with upregulation of fatty acid oxidation in the kidney of high fructose-fed rats

2020 ◽  
Vol 318 (3) ◽  
pp. F826-F834
Author(s):  
Gaizun Hu ◽  
Lusi Xu ◽  
Yixuan Ma ◽  
Masahiro Kohzuki ◽  
Osamu Ito
Keyword(s):  
Renal Function ◽  
Fatty Acid ◽  
Lipid Accumulation ◽  
Binding Protein ◽  
Regulatory Element ◽  
High Fructose ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Acyl Coa Oxidase ◽  
Renal Expression

Excessive fructose intake causes metabolic syndrome and lipid accumulation in the kidney and leads to renal dysfunction and damage. Exercise (Ex) improves lipids regulation, but the mechanisms are unclarified in the kidney. In the present study, male Sprague-Dawley rats were allocated to groups fed with control or high-fructose (HFr) diet. Part of rats in each group underwent aerobic treadmill Ex for 12 wk. Drug treatment was performed as the fenofibrate gavage during the last 4 wk on HFr diet-fed rats. Renal function, histological changes, and expression of regulators involved in fatty acid (FA) metabolism were assessed. In CON diet-fed groups, Ex did not affect renal function or histology and significantly increased renal expression of FA β-oxidation regulators including acyl-CoA dehydrogenases (CADs), acyl-CoA oxidase, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-γ coactivator (PGC)-1α and lipogenic factors including acetyl-CoA carboxylase (ACCα), FA synthase (FAS), and sterol regulatory element-binding protein 1c. HFr caused albuminuria, lipid accumulation, and renal pathohistological changes, which were attenuated by Ex but not by fenofibrate. HFr decreased renal expression of medium- and short-chain CADs and PPAR-α and increased renal expression of ACCα, FAS, and sterol regulatory element-binding protein 1c. Ex increased expression of CADs, carnitine palmitoyltransferase type I, acyl-CoA oxidase, PPAR-α, and PGC-1α and decreased renal expression of ACCα and FAS in HFr diet-fed rats. The Ex-induced FA metabolism alteration was similar to that in the fenofibrate-treated group. In conclusion, the present study indicates that Ex enhanced renal FA metabolism, which might protect the kidney in lipid dysregulation diseases.

Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c

2003 ◽  
Vol 282 (2) ◽  
pp. 132-137 ◽  
Author(s):  
Y.u-A.n Yang ◽  
Patrice J. Morin ◽  
Wan Fang Han ◽  
Tinghua Chen ◽  
Daniel M. Bornman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals Dietaryα-lactalbumin induced fatty liver by enhancing nuclear liver X receptorαβ/sterol regulatory element-binding protein-1c/PPARγexpression and minimising PPARα/carnitine palmitoyltransferase-1 expression and AMP-activated protein kinaseαphosphorylation associated with atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c mice

2017 ◽  
Vol 118 (11) ◽  
pp. 914-929 ◽  
Author(s):  
María Elvira López-Oliva ◽  
Alba Garcimartin ◽  
Emilia Muñoz-Martínez
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Fatty Acid ◽  
Regulatory Element ◽  
Liver Steatosis ◽  
Element Binding Protein ◽  
Atherogenic Dyslipidaemia ◽  
Sterol Regulatory Element ◽  
Carnitine Palmitoyltransferase 1 ◽  
And Oxidative Stress

AbstractThe effect and the role played by dietaryα-lactalbumin (α-LAC) on hepatic fat metabolism are yet to be fully elucidated. We reported previously thatα-LAC intake induced atherogenic dyslipidaemia in Balb/c mice. The aim of the present study was to investigate if this atherogenic effect could be due to a possibleα-LAC-induced hepatic steatosis. We examine the ability of dietaryα-LAC to induce liver steatosis, identifying the molecular mechanisms underlying hepatic lipid metabolism in association with the lipid profile, peripheral insulin resistance (IR) and changes in the hepatic oxidative environment. Male Balb/c mice (n6) were fed with diets containing either chow or 14 %α-LAC for 4 weeks. Theα-LAC-fed mice developed abdominal adiposity and IR. Moderate liver steatosis with increased TAG and NEFA contents was correlated with atherogenic dyslipidaemia. There was increased nuclear expression of liver X receptorαβ(LXRαβ), sterol regulatory element-binding protein-1c (SREBP-1c) and PPARγtranscription factors and of the cytosolic enzymes acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase involved in the hepaticde novolipogenesis. The opposite was found for the nuclear receptor PPARαand the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT-1), leading to reduced fatty acidβ-oxidation (FAO). These changes were associated with a significant decrease in both p-Thr172-AMP-activated protein kinaseα(AMPKα) (inactivation) and p-Ser79-ACC1 (activation) and with a more oxidative liver environment increasing lipid peroxidation and protein oxidation and reducing GSH:GSSG ratio in theα-LAC-fed mice. In conclusion, 4 weeks of 14 %α-LAC feeding induced liver steatosis associated with atherogenic dyslipidaemia, IR and oxidative stress by enhancing nuclear LXRαβ/SREBP-1c/PPARγexpression and diminishing PPARα/CPT-1 expression and AMPKαphosphorylation shifting the hepatic FAO toward fatty acid synthesis in Balb/c mice.

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