Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase CGI-58

Badin, Pierre-Marie; Loubière, Camille; Coonen, Maarten; Louche, Katie; Tavernier, Geneviève; Bourlier, Virginie; Mairal, Aline; Rustan, Arild C.; Smith, Steven R.; Langin, Dominique; Moro, Cédric

doi:10.1194/jlr.m019182

Cited by 45 publications

(44 citation statements)

References 42 publications

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“…Taken together, these data suggest that the substantial increase in SM TG levels is caused by impaired TG catabolism, which is compensated by increased FA influx (increased LPL and CD36 mRNA) and glucose utilization (increased RQ). Such a conclusion is in line with a recent study reporting that the knockdown of CGI-58 in differentiated human myotubes markedly reduced TG catabolism and increased glucose oxidation (40).…”

Section: Discussionsupporting

confidence: 80%

Functional Cardiac Lipolysis in Mice Critically Depends on Comparative Gene Identification-58

Zierler

Jaeger

Pollak

et al. 2013

Journal of Biological Chemistry

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Background:The role of CGI-58 in muscle triacylglycerol catabolism is unknown. The presence of CGI-58 increases the lipolytic activity of adipose triglyceride lipase (ATGL). Results: Muscle-specific CGI-58 deficiency causes muscle steatosis and cardiac dysfunction despite elevated ATGL protein expression. Conclusion: Muscle lipolysis critically depends on both CGI-58 and ATGL. Significance: Muscle CGI-58 deficiency provokes severe cardiac steatosis and dysfunction.

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Section: Discussionsupporting

confidence: 80%

Functional Cardiac Lipolysis in Mice Critically Depends on Comparative Gene Identification-58

Zierler

Jaeger

Pollak

et al. 2013

Journal of Biological Chemistry

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“…We and others previously described a cGMP-dependent induction of PGC1a gene expression by NP in white fat and skeletal muscle cells (19,20). PPARd can be activated by lipid ligands derived from endogenous TAG lipolysis (31,44).…”

Section: Discussionmentioning

confidence: 92%

“…Pulse-chase experiments to determine lipolytic flux and oleate incorporation into total lipids, triacylglycerols (TAGs), and diacylglycerols (DAGs) by thin-layer chromatography were performed as previously described (31). Incorporation rates were normalized to total protein content in each well.…”

Section: Determination Of Fatty Acid Metabolismmentioning

confidence: 99%

Defective Natriuretic Peptide Receptor Signaling in Skeletal Muscle Links Obesity to Type 2 Diabetes

et al. 2015

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Circulating natriuretic peptide (NP) levels are reduced in obesity and predict the risk of type 2 diabetes (T2D). Since skeletal muscle was recently shown as a key target tissue of NP, we aimed to investigate muscle NP receptor (NPR) expression in the context of obesity and T2D. Muscle NPRA correlated positively with wholebody insulin sensitivity in humans and was strikingly downregulated in obese subjects and recovered in response to diet-induced weight loss. In addition, muscle NP clearance receptor (NPRC) increased in individuals with impaired glucose tolerance and T2D. Similar results were found in obese diabetic mice. Although no acute effect of brain NP (BNP) on insulin sensitivity was observed in lean mice, chronic BNP infusion improved blood glucose control and insulin sensitivity in skeletal muscle of obese and diabetic mice. This occurred in parallel with a reduced lipotoxic pressure in skeletal muscle due to an upregulation of lipid oxidative capacity. In addition, chronic NP treatment in human primary myotubes increased lipid oxidation in a PGC1a-dependent manner and reduced palmitate-induced lipotoxicity. Collectively, our data show that activation of NPRA signaling in skeletal muscle is important for the maintenance of long-term insulin sensitivity and has the potential to treat obesity-related metabolic disorders.

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“…The up-regulated genes in lipid metabolism and fatty acid oxidation suggest that the GW501516-induced increase in fatty acid utilization could be the primary event, which in turn leads to an inhibition of glucose uptake and glucose oxidation via the well-known mutual inhibition of substrate metabolism in the glucose-fatty acid cycle (Randle et al, 1963). Moreover, GW501516 increased expression of PDK4, a key enzyme important in switching the fuel source from glucose to fatty acid (Badin et al, 2012;Dressel et al, 2003;Kramer et al, 2007;Kleiner et al, 2009). Increased PDK4 is coupled to reduced PDH activity and thereby reduced glucose oxidation (Badin et al, 2012).…”

Section: Discussionmentioning

confidence: 96%

“…Moreover, GW501516 increased expression of PDK4, a key enzyme important in switching the fuel source from glucose to fatty acid (Badin et al, 2012;Dressel et al, 2003;Kramer et al, 2007;Kleiner et al, 2009). Increased PDK4 is coupled to reduced PDH activity and thereby reduced glucose oxidation (Badin et al, 2012). PDK4 inhibition of glucose oxidation in response to elevated plasma fatty acid availability has been observed during fasting or high-fat feeding (Spriet et al, 2004), and this may reflect PPAR's role to promote utilization of fatty acids under physiological conditions, although it is not confirmed that the increased fatty acid levels during fasting regulate PPAR (de Lange et al, 2008;Ehrenborg & Krook, 2009).…”

Section: Discussionmentioning

confidence: 99%

PPARδ activation in human myotubes increases mitochondrial fatty acid oxidative capacity and reduces glucose utilization by a switch in substrate preference

Feng

Nikolić

Bakke

et al. 2013

Archives of Physiology and Biochemistry

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The role of peroxisome proliferator-activated receptor δ (PPARδ) activation on global gene expression and mitochondrial fuel utilization were investigated in human myotubes. Only 21 genes were up-regulated and 3 genes were down-regulated after activation by the PPARδ agonist GW501516. Pathway analysis showed up-regulated mitochondrial fatty acid oxidation, TCA cycle and cholesterol biosynthesis. GW501516 increased oleic acid oxidation and mitochondrial oxidative capacity by 2-fold. Glucose uptake and oxidation were reduced, but total substrate oxidation was not affected, indicating a fuel switch from glucose to fatty acid. Cholesterol biosynthesis was increased, but lipid biosynthesis and mitochondrial content were not affected. This study confirmed that the principal effect of PPARδ activation was to increase mitochondrial fatty acid oxidative capacity. Our results further suggest that PPARδ activation reduced glucose utilization through a switch in mitochondrial substrate preference by up-regulating pyruvate dehydrogenase kinase isozyme 4 and genes involved in lipid metabolism and fatty acid oxidation.

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Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase CGI-58

Cited by 45 publications

References 42 publications

Functional Cardiac Lipolysis in Mice Critically Depends on Comparative Gene Identification-58

Functional Cardiac Lipolysis in Mice Critically Depends on Comparative Gene Identification-58

Defective Natriuretic Peptide Receptor Signaling in Skeletal Muscle Links Obesity to Type 2 Diabetes

PPARδ activation in human myotubes increases mitochondrial fatty acid oxidative capacity and reduces glucose utilization by a switch in substrate preference

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