Adipose Triglyceride Lipase and Hormone-Sensitive Lipase Protein Expression Is Decreased in the Obese Insulin-Resistant State

Jocken, Johan W. E.; Langin, Dominique; Smit, Egbert F.; Saris, Wim H. M.; Valle, Carine; Hul, Gabby B.; Holm, Cecilia; Arner, Peter; Blaak, Ellen E.

doi:10.1210/jc.2006-1318

Cited by 230 publications

(204 citation statements)

References 41 publications

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“…Cycs and Cox5b) were downregulated in mice fed high-fat diets compared with those fed standard diets (Fig. 6f), consistent with previous reports [8,[29][30][31]. Treatment with CZ5 restored the impaired expression of these genes, with the exception of Fasn mRNA, which was further decreased.…”

Section: I)supporting

confidence: 90%

A novel chemical uncoupler ameliorates obesity and related phenotypes in mice with diet-induced obesity by modulating energy expenditure and food intake

Zhang

Turner

et al. 2013

Diabetologia

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Aims/hypothesis Decreasing mitochondrial coupling efficiency has been shown to be an effective therapy for obesity and related metabolic symptoms. Here we identified a novel mitochondrial uncoupler that promoted uncoupled respiration in a cell type-specific manner and investigated its effects on modulation of energy metabolism in vivo and in vitro. Methods We screened a collection of mitochondrial membrane potential depolarising compounds for a novel chemical uncoupler on isolated skeletal muscle mitochondria using a channel oxygen system. The effect on respiration of metabolic cells (L6 myotubes, 3T3-L1 adipocytes and rat primary hepatocytes) was examined and metabolic pathways sensitive to cellular ATP content were also evaluated. The chronic metabolic effects were investigated in high-fat diet-induced obese mice and standard diet-fed (SD) lean mice.Results The novel uncoupler, CZ5, promoted uncoupled respiration in a cell type-specific manner. It stimulated fuel oxidation in L6 myotubes and reduced lipid accumulation in 3T3-L1 adipocytes but did not affect gluconeogenesis or the triacylglycerol content in hepatocytes. The administration of CZ5 to SD mice increased energy expenditure (EE) but did not affect body weight or adiposity. Chronic studies in mice on high-fat diet showed that CZ5 reduced body weight and improved glucose and lipid metabolism via both increased EE and suppressed energy intake. The reduced adiposity was associated with the restoration of expression of key metabolic genes in visceral adipose tissue. Conclusions/interpretation This work demonstrates that a cell type-specific mitochondrial chemical uncoupler may have therapeutic potential for treating high-fat diet-induced metabolic diseases.

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Section: I)supporting

confidence: 90%

A novel chemical uncoupler ameliorates obesity and related phenotypes in mice with diet-induced obesity by modulating energy expenditure and food intake

Zhang

Turner

et al. 2013

Diabetologia

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“…Taking into account the fact that obese people have low-grade inflammation (Heilbronn and Campbell 2008), the increased expression of ATGL in obese people may be due to the increased inflammation, and the reduction in ATGL mRNA levels when obese people lose weight (Jocken et al 2007;Viguerie et al 2005) may be explained by a reduction or disappearance of the low-grade inflammation because of the reduction in body weight. These observations, together with the positive correlation found between ATGL mRNA and plasma TNF-a levels, support the idea of inflammation as the agent responsible for ATGL dysregulation.…”

Section: Discussionmentioning

confidence: 99%

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients

et al. 2014

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Adipose tissue (AT) is a key organ in the regulation of total body lipid homeostasis, which is responsible for the storage and release of fatty acids according to metabolic needs. We aimed to investigate the effect of the quantity and quality of dietary fat on the lipogenesis and lipolysis processes in the AT of metabolic syndrome (MetS) patients. A randomized, controlled trial conducted within the LIPGENE study assigned MetS patients to one of four diets: (a) high-saturated fatty acid (HSFA) (b) highmonounsaturated fatty acid, and (c, d) two low-fat, highcomplex carbohydrate diets supplemented with long chain (LC) n-3 (LFHCC n-3) polyunsaturated fatty acids (PUFA) or placebo (LFHCC), for 12 weeks each. A fat challenge reflecting the same fatty acid composition as the original diets was conducted post-intervention. Long-term consumption of the LFHCC diet induced an increase in the fasting expression levels of the sterol regulatory element binding protein-1 and stearoyl-CoA desaturase D9-desaturase genes, whereas the supplementation of this diet with n-3 PUFA reversed this effect (p = 0.007). In contrast, long-term consumption of the HSFA diet increased the expression of the adipose triglyceride lipase (ATGL) gene, at both fasting and postprandial states (both, p \ 0.001). Our results showed the anti-lipogenic effect exerted by LC n-3 PUFA when administered together with a LFHCC diet. Conversely, a diet high in saturated fat increased the expression of the lipolytic gene ATGL relative to the other diets.

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“…ATGL is the causative gene of triglyceride deposit cardiomyovasculopathy, which is characterized by massive accumulation of TG in the coronary arteries and myocardium and leads to chronic heart failure (24). Additionally, in patients with prediabetes or diabetes, ATGL protein expression and TG lipase activity are both reduced (5,6). Therefore, we investigated whether decreased ATGL activity may affect several biomolecules involved in the process of atherosclerosis in vitro.…”

Section: Discussionmentioning

confidence: 99%

Reduced Expression of Adipose Triglyceride Lipase Enhances Tumor Necrosis Factor α-induced Intercellular Adhesion Molecule-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C-dependent Activation of Nuclear Factor-κB

Inoue

Kobayashi

Inoguchi

et al. 2011

Journal of Biological Chemistry

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Background: Adipose triglyceride lipase (ATGL) expression is decreased in the obese insulin-resistant state. Results: RNA interference-mediated down-regulation of ATGL enhanced monocyte adhesion via increased expression of tumor necrosis factor ␣-induced intercellular adhesion molecule-1. Conclusion: Reduced ATGL expression may influence the atherogenic process in the insulin-resistant state. Significance: This mechanism also leads to the acceleration of atherosclerosis in patients with insulin-resistance, even if not in a state of hyperglycemia.

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Adipose Triglyceride Lipase and Hormone-Sensitive Lipase Protein Expression Is Decreased in the Obese Insulin-Resistant State

Abstract: In obese subjects, insulin resistance and hyperinsulinemia are strongly associated with ATGL and HSL mRNA and protein expression, independent of fat mass. Data on weight reduction indicated that also other factors (e.g. leptin) relate to ATGL and HSL protein expression.

Cited by 230 publications

References 41 publications

A novel chemical uncoupler ameliorates obesity and related phenotypes in mice with diet-induced obesity by modulating energy expenditure and food intake

A novel chemical uncoupler ameliorates obesity and related phenotypes in mice with diet-induced obesity by modulating energy expenditure and food intake

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients

Reduced Expression of Adipose Triglyceride Lipase Enhances Tumor Necrosis Factor α-induced Intercellular Adhesion Molecule-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C-dependent Activation of Nuclear Factor-κB

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