Sterol-regulatory-element-binding protein I c mediates insulin action on hepatic gene expression

Ferré, Pascal; Foretz, Marc; Azzout‐Marniche, Dalila; Becard, Dominique; Foufelle, Fabienne

doi:10.1042/bst0290547

Cited by 28 publications

(11 citation statements)

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“…Since Srebp-1c plays a crucial role in insulin-mediated de novo lipogenesis in the liver [30], it is well possible that the improved HFD-induced glucose intolerance accompanied by reduced insulin levels resulted in downregulation of hepatic Srebp-1c expression, thereby attenuating the HFD-induced increase in de novo lipogenesis. Beside insulin levels, Pgc1β could also be involved as it impacts on Srebp-1c expression [31].…”

Section: Discussionmentioning

confidence: 99%

GLP-1 Receptor Activation Inhibits VLDL Production and Reverses Hepatic Steatosis by Decreasing Hepatic Lipogenesis in High-Fat-Fed APOE*3-Leiden Mice

et al. 2012

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ObjectiveIn addition to improve glucose intolerance, recent studies suggest that glucagon-like peptide-1 (GLP-1) receptor agonism also decreases triglyceride (TG) levels. The aim of this study was to evaluate the effect of GLP-1 receptor agonism on very-low-density lipoprotein (VLDL)-TG production and liver TG metabolism.Experimental ApproachThe GLP-1 peptide analogues CNTO3649 and exendin-4 were continuously administered subcutaneously to high fat diet-fed APOE*3-Leiden transgenic mice. After 4 weeks, hepatic VLDL production, lipid content, and expression profiles of selected genes involved in lipid metabolism were determined.ResultsCNTO3649 and exendin-4 reduced fasting plasma glucose (up to −30% and −28% respectively) and insulin (−43% and −65% respectively). In addition, these agents reduced VLDL-TG production (−36% and −54% respectively) and VLDL-apoB production (−36% and −43% respectively), indicating reduced production of VLDL particles rather than reduced lipidation of apoB. Moreover, they markedly decreased hepatic content of TG (−39% and −55% respectively), cholesterol (−30% and −55% respectively), and phospholipids (−23% and −36% respectively), accompanied by down-regulation of expression of genes involved in hepatic lipogenesis (Srebp-1c, Fasn, Dgat1) and apoB synthesis (Apob).ConclusionGLP-1 receptor agonism reduces VLDL production and hepatic steatosis in addition to an improvement of glycemic control. These data suggest that GLP-receptor agonists could reduce hepatic steatosis and ameliorate dyslipidemia in patients with type 2 diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

GLP-1 Receptor Activation Inhibits VLDL Production and Reverses Hepatic Steatosis by Decreasing Hepatic Lipogenesis in High-Fat-Fed APOE*3-Leiden Mice

et al. 2012

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“…An increase in suppressors of cytokine signaling-3 in the liver leads to persistent hyperinsulinemia, which further exacerbates insulin resistance. 37 Hyperinsulinemia stimulates the transcription factor sterol regulatory element-binding protein-1c, 38 which leads to activation of lipogenic genes and a decrease in fatty oxidation. Additional overproduction of fatty acid and continued lipotoxicity result in further insulin resistance, creating a vicious cycle.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Risk Factors and the Metabolic Syndrome in Pediatric Nonalcoholic Fatty Liver Disease

et al. 2008

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Background-Nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease in children, is associated with obesity and insulin resistance. However, the relationship between NAFLD and cardiovascular risk factors in children is not fully understood. The objective of this study was to determine the association between NAFLD and the presence of metabolic syndrome in overweight and obese children. Methods and Results-This case-control study of 150 overweight children with biopsy-proven NAFLD and 150 overweight children without NAFLD compared rates of metabolic syndrome using Adult Treatment Panel III criteria. Cases and controls were well matched in age, sex, and severity of obesity. Children with NAFLD had significantly higher fasting glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure than overweight and obese children without NAFLD. Subjects with NAFLD also had significantly lower high-density lipoprotein cholesterol than controls. After adjustment for age, sex, race, ethnicity, body mass index, and hyperinsulinemia, children with metabolic syndrome had 5.0 (95% confidence interval, 2.6 to 9.7) times the odds of having NAFLD as overweight and obese children without metabolic syndrome. Conclusions-NAFLD in overweight and obese children is strongly associated with multiple cardiovascular risk factors.The identification of NAFLD in a child should prompt global counseling to address nutrition, physical activity, and avoidance of smoking to prevent the development of cardiovascular disease and type 2 diabetes. (Circulation. 2008; 118:277-283.)

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“…Both in the fed and fasted state, G6P dehydrogenase (G6PDH) and Taldo expression levels were lower in PPAR α −/− mice and during refeeding, induction of glucokinase expression was blunted [35]. Because SREBP-1c is a major mediator of insulin action on hepatic glycolytic and lipogenic gene expression [59], lower SREBP-1c expression levels in liver of PPAR α −/− mice also point to reduced hepatic insulin sensitivity. …”

Section: Pparα and Hepatic Insulin Sensitivitymentioning

confidence: 99%

Role of PPAR in Hepatic Carbohydrate Metabolism

Peeters

Baes

2010

PPAR Research

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Tight control of storage and synthesis of glucose during nutritional transitions is essential to maintain blood glucose levels, a process in which the liver has a central role. PPARα is the master regulator of lipid metabolism during fasting, but evidence is emerging for a role of PPARα in balancing glucose homeostasis as well. By using PPARα ligands and PPARα −/− mice, several crucial genes were shown to be regulated by PPARα in a direct or indirect way. We here review recent evidence that PPARα contributes to the adaptation of hepatic carbohydrate metabolism during the fed-to-fasted or fasted-to-fed transition in rodents.

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Sterol-regulatory-element-binding protein I c mediates insulin action on hepatic gene expression

Cited by 28 publications

References 1 publication

GLP-1 Receptor Activation Inhibits VLDL Production and Reverses Hepatic Steatosis by Decreasing Hepatic Lipogenesis in High-Fat-Fed APOE*3-Leiden Mice

GLP-1 Receptor Activation Inhibits VLDL Production and Reverses Hepatic Steatosis by Decreasing Hepatic Lipogenesis in High-Fat-Fed APOE*3-Leiden Mice

Cardiovascular Risk Factors and the Metabolic Syndrome in Pediatric Nonalcoholic Fatty Liver Disease

Role of PPAR in Hepatic Carbohydrate Metabolism

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