A PGC-1α Isoform Induced by Resistance Training Regulates Skeletal Muscle Hypertrophy

Ruas, Jorge L.; White, James P.; Rao, Rajesh R.; Kleiner, Sandra; Brannan, Kevin T.; Harrison, Brooke C.; Greene, Nicholas P.; Wu, Jun; Estall, Jennifer L.; Irving, Brian A.; Lanza, Ian R.; Rasbach, Kyle A.; Okutsu, Mitsuharu; Nair, K. Sreekumaran; Yan, Zhen; Leinwand, Leslie A.; Spiegelman, Bruce M.

doi:10.1016/j.cell.2012.10.050

Cited by 568 publications

(832 citation statements)

References 44 publications

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“…Consistent with their nomenclature, the canonical isoform was renamed Pgc-1α1. The alternative gene promoter is highly conserved between species and has been shown to be active in human skeletal muscle [34][35][36]. Accordingly, the novel PGC-1α isoforms are detected in skeletal muscle after exercise [35][36][37].…”

Section: Where Do We Start? Multiple Origins For Pgc-1α Transcriptsmentioning

confidence: 96%

“…Two studies showed that stimulation of BAT [46] or skeletal muscle [47] shifts promoter activation, favouring the expression of either full-length or NT-PGC-1α from the novel upstream gene promoter [33]. In this way, the repertoire of Pgc-1α isoforms is increased by the addition of two NT-Pgc-1α variants that contain both versions of the novel exon 1b, namely NT-Pgc-1α-b (which is identical to Pgc-1α4, described by Ruas et al in 2012 [36]) and NT-Pgc-1α-c. Consequently, NT-PGC-1α was renamed NT-PGC-1α-a.…”

Section: Nt(erminal)-pgc-1αmentioning

confidence: 97%

“…1) results in the transcription of three additional PGC-1α variants with unique structural features [36]. Two of these variants, Pgc-1α2 and Pgc-1α3, share with Pgc-1α-b and Pgc-1α-c (respectively) the splice variants of exon 1b, but differ vastly in structure from any of the other isoforms (Fig.…”

Section: Nt(erminal)-pgc-1αmentioning

confidence: 99%

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The hitchhiker’s guide to PGC-1α isoform structure and biological functions

2015

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Proteins of the peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1 (PGC-1) family of transcriptional coactivators coordinate physiological adaptations in many tissues, usually in response to demands for higher nutrient and energy supply. Of the founding members of the family, PGC-1α (also known as PPARGC1A) is the most highly regulated gene, using multiple promoters and alternative splicing to produce a growing number of coactivator variants. PGC-1α promoters are selectively active in distinct tissues in response to specific stimuli. To date, more than ten novel PGC-1α isoforms have been reported to be expressed from a novel promoter (PGC-1α-b, PGC-1α-c), to undergo alternative splicing (NT-PGC-1α) or both (PGC-1α2, PGC-1α3, PGC-1α4). The resulting proteins display differential regulation and tissue distribution and, most importantly, exert specific biological functions. In this review we discuss the structural and functional characteristics of the novel PGC-1α isoforms, aiming to provide an integrative view of this constantly expanding system of transcriptional coactivators.

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Section: Where Do We Start? Multiple Origins For Pgc-1α Transcriptsmentioning

confidence: 96%

Section: Nt(erminal)-pgc-1αmentioning

confidence: 97%

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The hitchhiker’s guide to PGC-1α isoform structure and biological functions

2015

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“…51,57 Meteorin-like (Metrnl) Metrnl was identified from primary myotubes overexpressing PGC1a4 40 , the PGC1a splice isoform that had been shown to regulates muscle hypertrophy and energy expenditure. 58 Increasing circulating Metrnl by 5-6-fold in mice by injection of adenoviral vectors increased whole-body energy expenditure, an effect associated with an increase in beiging of scWAT. 40 In addition, administration of an anti-Metrnl antibody partially prevented cold-induced beiging of scWAT, suggesting that Metrnl could be an important hormone mediating the beiging phenotype.…”

Section: Myostatinmentioning

confidence: 99%

Exercise regulation of adipose tissue

2016

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Exercise training results in adaptations to numerous organ systems and offers protection against metabolic disorders including obesity and type 2 diabetes, and recent reports suggest that adipose tissue may play a role in these beneficial effects of exercise on overall health. Multiple studies have investigated the effects of exercise training on both white adipose tissue (WAT) and brown adipose tissue (BAT), as well as the induction of beige adipocytes. Studies from both rodents and humans show that there are exercise training-induced changes in WAT including decreased cell size and lipid content, and increased mitochondrial activity. In rodents, exercise training causes an increased beiging of WAT. Whether exercise training causes a beiging of human scWAT, as well as which factors contribute to the exercise-induced beiging of WAT are areas of current investigation. Studies investigating the effects of exercise training on BAT mass and function have yielded conflicting data, and hence, is another area of intensive investigation. This review will focus on studies aimed at elucidating the mechanisms regulating exercise training induced-adaptations to adipose tissue.

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“…Myostatin is upregulated in obesity and downregulated by exercise 9, 10, 11, 12. Targeted inhibition of myostatin, genetically or pharmaceutically, has had promising results in improving cardiometabolic health (namely, glucose tolerance) and preventing/restoring muscle mass in rodents and humans 8, 13, 14, 15, 16, 17, 18…”

Section: Introductionmentioning

confidence: 99%

Increased Muscle Mass Protects Against Hypertension and Renal Injury in Obesity

Butcher

Mintz

Larion

et al. 2018

JAHA

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BackgroundObesity compromises cardiometabolic function and is associated with hypertension and chronic kidney disease. Exercise ameliorates these conditions, even without weight loss. Although the mechanisms of exercise's benefits remain unclear, augmented lean body mass is a suspected mechanism. Myostatin is a potent negative regulator of skeletal muscle mass that is upregulated in obesity and downregulated with exercise. The current study tested the hypothesis that deletion of myostatin would increase muscle mass and reduce blood pressure and kidney injury in obesity.Methods and ResultsMyostatin knockout mice were crossed to db/db mice, and metabolic and cardiovascular functions were examined. Deletion of myostatin increased skeletal muscle mass by ≈50% to 60% without concomitant weight loss or reduction in fat mass. Increased blood pressure in obesity was prevented by the deletion of myostatin, but did not confer additional benefit against salt loading. Kidney injury was evident because of increased albuminuria, which was abolished in obese mice lacking myostatin. Glycosuria, total urine volume, and whole kidney NOX‐4 levels were increased in obesity and prevented by myostatin deletion, arguing that increased muscle mass provides a multipronged defense against renal dysfunction in obese mice.ConclusionsThese experimental observations suggest that loss of muscle mass is a novel risk factor in obesity‐derived cardiovascular dysfunction. Interventions that increase muscle mass, either through exercise or pharmacologically, may help limit cardiovascular disease in obese individuals.

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A PGC-1α Isoform Induced by Resistance Training Regulates Skeletal Muscle Hypertrophy

Cited by 568 publications

References 44 publications

The hitchhiker’s guide to PGC-1α isoform structure and biological functions

The hitchhiker’s guide to PGC-1α isoform structure and biological functions

Exercise regulation of adipose tissue

Increased Muscle Mass Protects Against Hypertension and Renal Injury in Obesity

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