Cold-induced PGC-1α expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway

Oliveira, Rachel L. G. S.; Ueno, Mirian; Souza, Cláudio Teodoro de; Pereira-da-Silva, Márcio; Gasparetti, Alessandra L.; Bezzera, Rosangela M. N.; Alberici, Luciane C.; Vercesi, Anı́bal E.; Saad, Mário J.A.; Velloso, Lı́cio A.

doi:10.1152/ajpendo.00103.2004

Cited by 60 publications

(59 citation statements)

References 51 publications

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“…The PGC-1α protein level was increased throughout cold acclimation (45 days) starting from day 3 of cold exposure. This is in accordance with previous data that showed that both short-term (4 days) and long-term (4-5 weeks) cold exposure induced PGC-1α expression in skeletal muscle (Oliveira et al, 2004;Bruton et al, 2010). PGC-1α regulates several key processes of adaptive thermogenesis in skeletal muscle, including fuel utilization and switching, insulin sensitivity, glucose transport, gluconeogenesis and lipid oxidation, mitochondrial content and function, ATP synthesis and muscle fiber differentiation Jäger et al, 2007).…”

Section: P<0001 Pgc-1α/ppars In Skeletal Muscle In the Coldsupporting

confidence: 93%

Regulatory role of PGC-1alpha/PPARs signaling in skeletal muscle metabolic recruitment during cold acclimation

Stančić

Buzadžić

Korać

et al. 2013

Journal of Experimental Biology

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SUMMARYThis study examined the molecular basis of energy-related regulatory mechanisms underlying metabolic recruitment of skeletal muscle during cold acclimation and possible involvement of the L-arginine/nitric oxide-producing pathway. Rats exposed to cold (4±1°C) for periods of 1, 3, 7, 12, 21 and 45 days were divided into three groups: untreated, L-arginine treated and N ω -nitro-Larginine methyl ester (L-NAME) treated. Compared with controls (22±1°C), there was an initial increase in the protein level of 5′-AMP-activated protein kinase α (day 1), followed by an increase in peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and peroxisome proliferator-activated receptors (PPARs): PPARα and PPARγ from day 1 and PPARδ from day 7 of cold acclimation. Activation of the PGC-1α/PPAR transcription program was accompanied by increased protein expression of the key metabolic enzymes in β-oxidation, the tricarboxylic acid cycle and oxidative phosphorylation, with the exceptions in complex I (no changes) and ATP synthase (decreased at day 1). Cold did not affect hexokinase and GAPDH protein levels, but increased lactate dehydrogenase activity compared with controls (1-45 days). L-arginine sustained, accelerated and/or intensified cold-induced molecular remodeling throughout cold acclimation. L-NAME exerted phase-dependent effects: similar to L-arginine in early cold acclimation and opposite after prolonged cold exposure (from day 21). It seems that upregulation of the PGC-1α/PPAR transcription program early during cold acclimation triggers the molecular recruitment of skeletal muscle underlying the shift to more oxidative metabolism during prolonged cold acclimation. Our results suggest that nitric oxide has a role in maintaining the skeletal muscle oxidative phenotype in late cold acclimation but question its role early in cold acclimation.

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Section: P<0001 Pgc-1α/ppars In Skeletal Muscle In the Coldsupporting

confidence: 93%

Regulatory role of PGC-1alpha/PPARs signaling in skeletal muscle metabolic recruitment during cold acclimation

Stančić

Buzadžić

Korać

et al. 2013

Journal of Experimental Biology

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“…2E). AMPK is a major regulator of skeletal muscle metabolism and has been shown to be activated to the phosphorylated form (p-AMPK) during conditions of increased energy demand including cold challenge (Koh et al, 2008;Kus et al, 2008;Oliveira et al, 2004). Upregulation of p-AMPK levels along with increased SERCA2a levels further indicate that muscle-based thermogenesis is increasingly recruited in the neonates in response to cold challenge.…”

Section: Resultsmentioning

confidence: 99%

Cold adaptation overrides developmental regulation of sarcolipin expression in mice skeletal muscle: SOS for muscle-based thermogenesis?

Pant

Bal

Periasamy

2015

Journal of Experimental Biology

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Neonatal mice have a greater thermogenic need than adult mice and may require additional means of heat production, other than the established mechanism of brown adipose tissue (BAT). We and others recently discovered a novel mediator of skeletal muscle-based thermogenesis called sarcolipin (SLN) that acts by uncoupling sarcoendoplasmic reticulum Ca 2+ -ATPase (SERCA). In addition, we have shown that SLN expression is downregulated during neonatal development in rats. In this study we probed two questions: (1) is SLN expression developmentally regulated in neonatal mice?; and (2) if so, will cold adaptation override this? Our data show that SLN expression is higher during early neonatal stages and is gradually downregulated in fast twitch skeletal muscles. Interestingly, we demonstrate that cold acclimation of neonatal mice can prevent downregulation of SLN expression. This observation suggests that SLN-mediated thermogenesis can be recruited to a greater extent during extreme physiological need, in addition to BAT.

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“…Cold and energy stress also induce the stress-activated protein kinase AMP-activated protein kinase (AMPK), which enhances EE and thus is a major target in obesity and T2D (19)(20)(21)(22)(23)(24). β-ARmediated AMPK activation augments insulin sensitivity in a UCP1-dependent manner (22).…”

Section: Introductionmentioning

confidence: 99%

Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis

Zhu

Ghoshal

Rodrigues

et al. 2016

Journal of Clinical Investigation

156

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Cold-induced PGC-1α expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway

Abstract: . Cold-induced PGC-1␣ expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway. Am J Physiol Endocrinol Metab

Cited by 60 publications

References 51 publications

Regulatory role of PGC-1alpha/PPARs signaling in skeletal muscle metabolic recruitment during cold acclimation

Regulatory role of PGC-1alpha/PPARs signaling in skeletal muscle metabolic recruitment during cold acclimation

Cold adaptation overrides developmental regulation of sarcolipin expression in mice skeletal muscle: SOS for muscle-based thermogenesis?

Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis

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