Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8336317 | The Journal of Nutritional Biochemistry | 2018 | 28 Pages |
Abstract
The prevalence of overweight and obesity in the population, along with their associated complications, is a major factor contributing to increased morbidity and mortality in developed countries. The liver is a vital organ for maintaining metabolic homeostasis, especially in the adjustment periods in fasting and feeding. Per-Arnt-Sim (PAS) kinase (PASK) controls glucose homeostasis and energy metabolism in response to nutritional status. PASK-deficient mice with a high-fat diet (HFD) resist the development of obesity and hepatic steatosis, with improved insulin sensitivity. We have investigated the regulation of the PASK expression in an HFD, as well as its role in adapting to fasting and feeding conditions. PASK-deficient mice with an HFD record improved parameters for the following: body weight, glucose tolerance, insulin resistance and serum lipid parameters. An HFD alters the down-regulation of Pask expression produced by fasting, as normally happens in a standard-fat diet. PASK deficiency blocks or diminishes the expression of many genes overexpressed in HFD-fed mice, such as the following: transcription factors involved in the regulation of gluconeogenic enzymes, the transport of fatty acid into mitochondria, beta-oxidation and de novo lipogenesis. PASK also regulates gene expression posttranscriptionally through the short noncoding RNAs involved in lipid metabolism and glucose homeostasis. The expression of miR-33a and miR-143 changes in PASK-deficient mice with an HFD. Thus, PASK-deficient mice improved their adaptation to feeding/fasting through a highly regulated molecular mechanism that controls the expression and function of the transcription factors, enzymes and miRNAs involved in glucose and insulin signaling.
Keywords
GCKRstearoyl-CoA desaturase-1SCD1PIP3G6PG6PaseChREBPPGC1αG6PDHPEPCKGCKPPARαDAPISFDSirtuin 2PI3KACCSREBP1cperoxisome proliferator-activated receptor γ coactivator 1αliver pyruvate kinaseL-PKFASFOXO1PPARγHFD4,6-diamidino-2-phenylindoleperoxisome proliferator-activated receptor alphaAkt/PKBacetyl coA carboxylasefatty acid synthasetriglyceridehigh-fat dietMedium-chain acyl-CoA dehydrogenasephosphatase and tensin homologphosphoenolpyruvate carboxykinaseLipogenesisHepatic metabolismObesityNADHnicotinamide adenine dinucleotidehexokinaseparaformaldehydeGlucokinase regulatory proteinForkhead box protein O1sterol regulatory element-binding protein 1cprotein kinase BPtencarnitine palmitoyltransferase 1aliver X receptor alphacarbohydrate-responsive element-binding proteinPeroxisome proliferator-activated receptor gammaGlucose 6-phosphateglucose 6-phosphate dehydrogenaseglucose 6-phosphataseGlucokinase
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Authors
Ana Pérez-GarcÃa, Pilar Dongil, Verónica Hurtado-Carneiro, Enrique Blázquez, Carmen Sanz, Elvira Álvarez,