Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids

Houten, Sander M.; Chegary, Malika; Brinke, Heleen te; Wijnen, Wino J.; Glatz, Jan F. C.; Luiken, Joost J. F. P.; Wijburg, Frits A.; Wanders, R. J. A.

doi:10.1007/s00018-009-9066-x

Cited by 49 publications

(47 citation statements)

References 44 publications

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“…PDK4 phosphorylates and inactivates the pyruvate dehydrogenase complex (PDH) during fasting, thereby decreasing glucose oxidation [28,41]. The glucose concentrations that were observed in this study are in line with this because there were no statistically significant differences in glucose levels after 24 h of fasting (online suppl.…”

Section: Discussionsupporting

confidence: 77%

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Changes in Gene Expression in PBMCs Profiles of PPARα Target Genes in Obese and Non-Obese Individuals During Fasting

Felicidade¹,

Marcarini

Carreira³

et al. 2014

Ann Nutr Metab

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Background: The prevalence of obesity has risen dramatically and the World Health Organization estimates that 700 million people will be obese worldwide by 2015. Approximately, 50% of the Brazilian population above 20 years of age is overweight, and 16% is obese. Aim: This study aimed to evaluate the differences in the expression of PPARα target genes in human peripheral blood mononuclear cells (PBMCs) and free fatty acids (FFA) in obese and non-obese individuals after 24 h of fasting. We first presented evidence that Brazilian people exhibit expression changes in PPARα target genes in PBMCs under fasting conditions. Methods: Q-PCR was utilized to assess the mRNA expression levels of target genes. Results: In both groups, the FFA concentrations increased significantly after 24 h of fasting. The basal FFA mean concentration was two-fold higher in the obese group compared with the non-obese group. After fasting, all genes evaluated in this study showed increased expression levels compared with basal expression in both groups. Conclusion: However, our results reveal no differences in gene expression between the obese and non-obese, more studies are necessary to precisely delineate the associated mechanisms, particularly those that include groups with different degrees of obesity and patients with diabetes mellitus type 2 because the expression of the main genes that are involved in β-oxidation and glucose level maintenance are affected by these factors. © 2014 S. Karger AG, Basel

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Section: Discussionsupporting

confidence: 77%

“…The entry of FFA into mitochondria is a regulated process. Blood glucose levels decrease concomitantly with a decrease in cellular glycolysis and CPT1 is activated permitting the mitochondrial entry of FFA [16,41]. Thus, fatty acids act as the main energy source for cells during fasting [28].…”

Section: Discussionmentioning

confidence: 99%

Changes in Gene Expression in PBMCs Profiles of PPARα Target Genes in Obese and Non-Obese Individuals During Fasting

Felicidade¹,

Marcarini

Carreira³

et al. 2014

Ann Nutr Metab

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“…would influence the greater induction observed in the in vivo model than in the C2C12 cells. With the induction of PDK4 (also observed by Houten et al [37] with oleate treatment in hepatoma cells and cardiomyocytes in vitro) the FA can play a direct role affecting the selection of fuel in order to spare glucose.…”

Section: Discussionmentioning

confidence: 99%

Time-course Effects of Increased Fatty Acid Supply on the Expression of Genes Involved in Lipid/Glucose Metabolism in Muscle Cells

Rodríguez

Sánchez

Tobaruela

et al. 2010

Cell Physiol Biochem

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Fatty acid (FA) oversupply in skeletal muscle is related with metabolic disorders associated to obesity, and also with normal physiological responses. We studied, in vivo and in vitro, the chronological response to physiological increases of FA, analyzing the expression of selected genes important for glucose/lipid metabolism. An in vivo sequential model of fasting (known to increase circulating FA) and refeeding was used in male Wistar rats to study soleus (more oxidative) and gastrocnemius (more glycolytic) muscles, and a chronological study was made in C2C12 muscle cells under treatment of oleic/linoleic FA mixture, at physiological concentration. Body weight, muscle glycogen and blood parameters (glucose, insulin, free fatty acids -FFA-, triglycerides) were monitored. mRNA levels of muscle carnitine palmitoyl transferase 1 (mCPT1), GLUT 4, insulin receptor (InsR), MyoD1, peroxisome proliferator activated receptor (PPAR) γ coactivator 1α (PGC1α) and β (PGC1β), PPARα, PPARδ, pyruvate dehydrogenase kinase 4 (PDK4) and uncoupling proteins (UCPs) 2 and 3 were analyzed by quantitative RT-PCR. The main results were the quick induction of PGC1α, UCP3 and PDK4 in vivo (more marked in gastrocnemius) and of PGC1α, PGC1β, InsR, PDK4, UCP2 and UCP3 in vitro. It is concluded that FA are able to rapidly induce the expression in muscle cells of key genes involved in their catabolism and that the oleic/linoleic acid mixture has a positive role increasing the expression of master metabolic regulators and their downstream target genes, facilitating the transition from a more glycolytic to a more lipid-oxidative metabolism.

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“…A low level of AMPK activation within the hypothalamus may be needed for lipid oxidation and torpor to continue, but high levels of AMPK activation will stimulate food intake and prevent torpor. For example, it appears that AMPK may be involved in this switch to fat utilization in heart muscle (Fryer and Carling, 2005;Houten et al, 2009). In the heart of hibernating thirteen-lined ground squirrels (Spermophilus tridecemlineatus), it has been shown that FFAs and insulin shift the fuel utilization within heart tissue by activating pyruvate dehydrogenase kinase isoenzyme 4 and this switch from carbohydrate to lipid metabolism is necessary for successful torpor and may require activated AMPK (Carey et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

To eat or not to eat: the effect of AICAR on food intake regulation in yellow-bellied marmots (Marmota flaviventris)

Florant

Fenn

Healy

et al. 2010

Journal of Experimental Biology

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SUMMARYMammals that hibernate (hibernators) exhibit a circannual rhythm of food intake and body mass. In the laboratory during the winter hibernation period, many hibernators enter a series of multi-day torpor bouts, dropping their body temperature to near ambient, and cease to feed even if food is present in their cage. The mechanism(s) that regulates food intake in hibernators is unclear. Recently, AMP-activated protein kinase (AMPK) has been shown to play a key role in the central regulation of food intake in mammals. We hypothesized that infusing an AMPK activator, 5-aminoimidazole-4-carboxamide 1 B-D-ribofuranoside (AICAR), intracerebroventricularly (ICV) into the third ventricle of the hypothalamus would stimulate yellow-bellied marmots (Marmota flaviventris) to feed during their hibernation season. Infusion of AICAR ICV into marmots at an ambient temperature of 22°C caused a significant (P<0.05) increase in food intake. In addition, animals stimulated to feed did not enter torpor during the infusion period. Marmots ICV infused with saline did not increase food intake and these animals continued to undergo torpor at an ambient temperature of 22°C. Our results suggest that AICAR stimulated the food intake pathway, presumably by activating AMPK. These results support the hypothesis that AMPK may be involved in regulating food intake in hibernators and that there may be common neural pathways involved in regulating feeding and eliciting torpor.

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Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids

Cited by 49 publications

References 44 publications

Changes in Gene Expression in PBMCs Profiles of PPARα Target Genes in Obese and Non-Obese Individuals During Fasting

Changes in Gene Expression in PBMCs Profiles of PPARα Target Genes in Obese and Non-Obese Individuals During Fasting

Time-course Effects of Increased Fatty Acid Supply on the Expression of Genes Involved in Lipid/Glucose Metabolism in Muscle Cells

To eat or not to eat: the effect of AICAR on food intake regulation in yellow-bellied marmots (Marmota flaviventris)

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