Exercise attenuates the fasting-induced transcriptional activation of metabolic genes in skeletal muscle

Hildebrandt, Audrey L.; Neufer, P. Darrell

doi:10.1152/ajpendo.2000.278.6.e1078

Cited by 80 publications

(89 citation statements)

References 43 publications

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“…A fasting-induced increase in mRNA levels of genes regulating the lipid metabolic pathway in skeletal muscle has been previously described [4][5][6], consistent with the observed increase in lipid metabolism in the tissue under fasting conditions. Given that SNF1 mediates transcriptional adaptations in yeast during glucose deprivation [1][2][3], we hypothesised that AMPK (a mammalian homologue of SNF1) may play a critical role in mediating a similar response in skeletal muscle during fasting.…”

Section: Discussionsupporting

confidence: 82%

“…One putative function of UCP3 is to export fatty acid anions from the mitochondrial matrix when acyl-CoA flux and lipid oxidation is increased [6,31,32] (Fig. 1).…”

Section: Genes Implicated In Lipid Metabolismmentioning

confidence: 99%

“…Under fed conditions, glucose is the main fuel source in skeletal muscle. However, during fasting, fuel use shifts to lipid metabolism, concomitantly with an increase in the expression of genes encoding proteins that regulate lipid metabolism, such as lipoprotein lipase (LPL), carnitine palmitoyl transferase-1 (CPT-1) and uncoupling protein 3 (UCP3) [4][5][6]. Thus, metabolic flexibility of skeletal muscle plays a central role in whole-body energy homeostasis and the pathogenesis of metabolic diseases such as type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

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Role of AMP-activated protein kinase in the coordinated expression of genes controlling glucose and lipid metabolism in mouse white skeletal muscle

Long

Barnes

Mahlapuu³

et al. 2005

Diabetologia

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Aims/hypothesis: AMP-activated protein kinase (AMPK) regulates metabolic adaptations in skeletal muscle. The aim of this study was to investigate whether AMPK modulates the expression of skeletal muscle genes that have been implicated in lipid and glucose metabolism under fed or fasting conditions. Methods: Two genetically modified animal models were used: AMPK γ3 subunit knockout mice (Prkag3 −/− ) and skeletal musclespecific transgenic mice (Tg-Prkag3225Q ) that express a mutant (R225Q) γ3 subunit. Levels of mRNA transcripts of genes involved in lipid and glucose metabolism in white gastrocnemius muscles of these mice (under fed or 16-h fasting conditions) were assessed by quantitative real-time PCR. Results: Wild-type mice displayed a coordinated increase in the transcription of skeletal muscle genes encoding proteins involved in lipid/oxidative metabolism (lipoprotein lipase, fatty acid transporter, carnitine palmitoyl transferase-1 and citrate synthase) and glucose metabolism (glycogen synthase and lactate dehydrogenase) in response to fasting. In contrast, these fasting-induced responses were impaired in Prkag3 −/− mice. The transcription of genes involved in lipid and oxidative metabolism was increased in the skeletal muscle of Tg-Prkag3 225Q mice compared with that in wild-type mice. Moreover, the expression of the genes encoding hexokinase II and 6-phosphofrucktokinase was decreased in Tg-Prkag3 225Q mice after fasting. Conclusions/ interpretation: AMPK is involved in the coordinated transcription of genes critical for lipid and glucose metabolism in white glycolytic skeletal muscle.

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Section: Discussionsupporting

confidence: 82%

“…One putative function of UCP3 is to export fatty acid anions from the mitochondrial matrix when acyl-CoA flux and lipid oxidation is increased [6,31,32] (Fig. 1).…”

Section: Genes Implicated In Lipid Metabolismmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of AMP-activated protein kinase in the coordinated expression of genes controlling glucose and lipid metabolism in mouse white skeletal muscle

Long

Barnes

Mahlapuu³

et al. 2005

Diabetologia

View full text Add to dashboard Cite

show abstract

“…PCR was performed using the following general cycle profile: 94°C for 5 min (94°C for 30 s, 56 -60°C for 30 s, 72°C for 30 s) ϫ cycle number, followed by a 72°C for 7-min extension. PCR primer pairs were designed from mouse-and rat-specific sequence data (GenBank TM ) except for LCAD (29). PCR cycle numbers were determined for each primer pair by extensive pretesting to optimize the conditions and that the product is with in the linear range of the PCR amplification (see Table I).…”

Section: Methodsmentioning

confidence: 99%

Peroxisome Proliferator-activated Receptor α (PPARα) Agonist Treatment Reverses PPARα Dysfunction and Abnormalities in Hepatic Lipid Metabolism in Ethanol-fed Mice

Fischer

You

Matsumoto

et al. 2003

Journal of Biological Chemistry

273

196

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Proper function of the peroxisome proliferator-activated receptor ␣ (PPAR␣) is essential for the regulation of hepatic fatty acid metabolism. Fatty acid levels are increased in liver during the metabolism of ethanol and should activate PPAR␣. However, recent in vitro data showed that ethanol metabolism inhibited the function of PPAR␣. We now report that ethanol feeding impairs fatty acid catabolism in the liver in part via blocking PPAR␣-mediated responses in C57BL/6J mice. Ethanol feeding decreased PPAR␣/retinoid X receptor ␣ binding in electrophoretic mobility shift assay of liver nuclear extracts. mRNAs for PPAR-regulated genes were reduced (long chain and medium chain acyl-CoA dehydrogenases) or failed to be induced (acyl-CoA oxidase, liver carnitine palmitoyl-CoA transferase, very long chain acyl-CoA synthetase, very long chain acyl-CoA dehydrogenase) in livers of the ethanol-fed animals, and ethanol feeding did not increase the rate of fatty acid ␤-oxidation. Wy14,643, a PPAR␣ agonist, restored the DNA binding activity of PPAR␣/retinoid X receptor ␣, induced mRNA levels of PPAR␣ target genes, stimulated the rate of fatty acid ␤-oxidation, and prevented fatty liver in ethanol-fed animals. Impairment of PPAR␣ function during ethanol consumption contributes to the development of alcoholic fatty liver, which can be overcome by Wy14,643.

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“…In mammals, much of the fasting response is transcriptionally regulated (7)(8)(9). Increased fat consumption is facilitated by the induction of genes involved in fatty acid ␤-oxidation, whereas repression of glycolysis genes and activation of gluconeogenic genes maintains glucose supply.…”

mentioning

confidence: 99%

A Caenorhabditis elegans nutrient response system partially dependent on nuclear receptor NHR-49

Gilst

Hadjivassiliou²,

Yamamoto³

2005

Proc. Natl. Acad. Sci. U.S.A.

249

285

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Appropriate response to nutritional stress is critical for animal survival and metabolic health. To better understand regulatory networks that sense and respond to nutritional availability, we developed a quantitative RT-PCR strategy to monitor changes in metabolic gene expression resulting from short-term food deprivation (fasting) in Caenorhabditis elegans. Examining 97 fat and glucose metabolism genes in fed and fasted animals, we identified 18 genes significantly influenced by food withdrawal in all developmental stages. Fasting response genes fell into multiple kinetic classes, with some genes showing significant activation or repression just 1 h after food was removed. As expected, fasting stimulated the expression of genes involved in mobilizing fats for energy production, including mitochondrial ␤-oxidation genes. Surprisingly, however, we found that other mitochondrial ␤-oxidation genes were repressed by food deprivation. Fasting also affected genes involved in mono-and polyunsaturated fatty acid synthesis: four desaturases were induced, and one stearoylCoA desaturase (SCD) was strongly repressed. Accordingly, fasted animals displayed considerable changes in fatty acid composition. Finally, nuclear receptor nhr-49 played a key role in nutritional response, enabling induction of ␤-oxidation genes upon food deprivation and facilitating activation of SCD in fed animals. Our characterization of a fasting response system and our finding that nhr-49 regulates a sector within this system provide insight into the mechanisms by which animals respond to nutritional signals.fasting ͉ fat metabolism ͉ HNF4 ͉ stearoyl-CoA desaturase P recise control of energy storage and consumption is essential for surviving periods of food deprivation. Regulatory networks that govern fat and glucose metabolism are optimized to expend carbohydrates and accumulate fat when food intake is abundant, and switch to the consumption of stored fat when food is scarce (1, 2). In mammals, an overnight fast stimulates fat breakdown for the production of energy, enabling maintenance of glucose supply for CNS function and yielding acetyl-CoA for ketone body synthesis (3, 4). Orchestration of the fasting response is critical, and mutations that disrupt it can cause potentially lethal hypoglycemia and hypoketonemia (4, 5). Indeed, even subtle misregulation of these pathways can bring about diabetes and obesity (1, 6).A complex network of hormonal signals and regulatory mechanisms governs adaptation to food availability. In mammals, much of the fasting response is transcriptionally regulated (7-9). Increased fat consumption is facilitated by the induction of genes involved in fatty acid ␤-oxidation, whereas repression of glycolysis genes and activation of gluconeogenic genes maintains glucose supply. Additionally, activation of ketogenic genes enhances conversion of fatty acid ␤-oxidation products into ketone bodies (3). Despite these general observations, studies of the fasting response have been limited to a select group of genes in only a subse...

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Exercise attenuates the fasting-induced transcriptional activation of metabolic genes in skeletal muscle

Cited by 80 publications

References 43 publications

Role of AMP-activated protein kinase in the coordinated expression of genes controlling glucose and lipid metabolism in mouse white skeletal muscle

Role of AMP-activated protein kinase in the coordinated expression of genes controlling glucose and lipid metabolism in mouse white skeletal muscle

Peroxisome Proliferator-activated Receptor α (PPARα) Agonist Treatment Reverses PPARα Dysfunction and Abnormalities in Hepatic Lipid Metabolism in Ethanol-fed Mice

A Caenorhabditis elegans nutrient response system partially dependent on nuclear receptor NHR-49

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