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

Abstract

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.

The AMP-activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-b-d-ribonucleoside, regulates lactate production in rat Sertoli cells

“…As for LDH isoenzyme system, Long et al (2005) have demonstrated a role of AMPK in the expression of LDH-B subunit in white skeletal muscle cells in mice. On the other hand, Putman et al (2003) have demonstrated that the long-term stimulation with AICAR reduces total LDH activity in skeletal muscle cells.…”

Role of AMP-activated protein kinase gamma 3 genetic variability in glucose and lipid metabolism in non-diabetic whites

“…On the other hand, PRKAG3-associated activity in skeletal muscle may also contribute to changes in LDLcholesterol serum levels. Beyond SREBP1 transcription [36], PRKAG3 regulates gene expression of various glucose-and lipid-metabolic key enzymes in white skeletal muscle [37] and therefore may have an effect on endogenous skeletal muscle cholesterol synthesis and LDL receptor expression. Such changes in cholesterol synthesis or LDL receptor expression of myocytes could alter their LDL-cholesterol ingestion, subsequently also altering serum LDL-cholesterol levels, as skeletal muscle tissue accounts for ∼5% of total peripheral LDL-cholesterol uptake [38,39].…”

Synergistic up-regulation of Hexokinase-2, glucose transporters and angiogenic factors in pancreatic cancer cells by glucose deprivation and hypoxia

“…Glucose deprivation has also been reported to activate an AMPK pathway [12], which enhances transcription of genes involved in lipid and glucose metabolism [13]. We have recently reported that glucose deprivation enhances the expressions of more than 60 genes including asparagines synthetase to protect the cells from apoptosis induced by glucose deprivation [14].…”