NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function

Yamamoto, Hiroyasu; Williams, Evan G.; Mouchiroud, Laurent; Cantó, Carles; Fan, Weiwei; Downes, Michael; Héligon, Christophe; Barish, Grant D.; Desvergne, Béatrice; Evans, Ronald M.; Schoonjans, Kristina; Auwerx, Johan

doi:10.1016/j.cell.2011.10.017

Cited by 239 publications

(308 citation statements)

References 68 publications

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“…The direct regulation of Plin5 by PPAR ␦ may therefore explain the uneven distribution of Plin5 expressed in muscle fi bers. Other factors found to drive formation of oxidative muscles includes PGC-1 ␣ ( 68 ), PGC-1 ␤ ( 69 ), ERR ␣ ( 70 ), ERR ␥ ( 71 ), and the corepressor NCoR1 ( 72 ). Overexpression of PGC-1 ␣ in muscle may stimulate Plin5 expression ( 73 ), but the importance of the other factors have not been studied.…”

Section: The Plin5 Intron 1 Contains An Evolutionary Conserved Pprementioning

confidence: 99%

Fatty acids regulate perilipin5 in muscle by activating PPARδ

Bindesbøll

Berg²,

Arntsen³

et al. 2013

Journal of Lipid Research

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Section: The Plin5 Intron 1 Contains An Evolutionary Conserved Pprementioning

confidence: 99%

Fatty acids regulate perilipin5 in muscle by activating PPARδ

Bindesbøll

Berg²,

Arntsen³

et al. 2013

Journal of Lipid Research

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“…Increased mitochondrial biogenesis is known to improve exercise performance (Rockl et al ., 2007; Yamamoto et al ., 2011). In the present investigation, using a mitochondrial DNA content assay, skeletal muscle of AC5 KO mice was shown to contain more mitochondria.…”

Section: Discussionmentioning

confidence: 99%

“…Ad‐AC5 shRNA was added to L6 rat skeletal muscle cells with 80% confluence, following 72–96 h of incubation. Real‐time O2 consumption rates (OCR) in L6 myoblast cells infected with either Ad‐AC5 shRNA or Ad‐LacZ were measured with Seahorse XF24 as described (Yamamoto et al ., 2011). …”

Section: Methodsmentioning

confidence: 99%

“…As enhanced exercise can result from mechanisms originating in either the heart or skeletal muscle, we examined cardiac and muscle function and also utilized tissue‐specific KOs in the heart and skeletal muscle. Skeletal muscle mitochondrial function (Yamamoto et al ., 2011), mitochondrial biogenesis (Irrcher et al ., 2003), and resistance to oxidative stress (Nishiyama et al ., 1998; Fisher‐Wellman et al ., 2009; Ryan et al ., 2010) were also examined, as these mechanisms mediate exercise performance (Rockl et al ., 2007). The SIRT1, FOXO3a, and MEK pathways, key to mitochondrial biogenesis and protection against oxidative stress, were also examined (Wu et al ., 1999; Lagouge et al ., 2006; Gurd et al ., 2009; Menzies et al ., 2013; Li et al ., 2015; Smith et al ., 2015).…”

Section: Introductionmentioning

confidence: 99%

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Type 5 adenylyl cyclase disruption leads to enhanced exercise performance

et al. 2015

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SummaryThe most important physiological mechanism mediating enhanced exercise performance is increased sympathetic, beta adrenergic receptor (β‐AR), and adenylyl cyclase (AC) activity. This is the first report of decreased AC activity mediating increased exercise performance. We demonstrated that AC5 disruption, that is, knock out (KO) mice, a longevity model, increases exercise performance. Importantly for its relation to longevity, exercise was also improved in old AC5 KO. The mechanism resided in skeletal muscle rather than in the heart, as confirmed by cardiac‐ and skeletal muscle‐specific AC5 KO's, where exercise performance was no longer improved by the cardiac‐specific AC5 KO, but was by the skeletal muscle‐specific AC5 KO, and there was no difference in cardiac output during exercise in AC5 KO vs. WT. Mitochondrial biogenesis was a major mechanism mediating the enhanced exercise. SIRT1, FoxO3a, MEK, and the anti‐oxidant, MnSOD were upregulated in AC5 KO mice. The improved exercise in the AC5 KO was blocked with either a SIRT1 inhibitor, MEK inhibitor, or by mating the AC5 KO with MnSOD hetero KO mice, confirming the role of SIRT1, MEK, and oxidative stress mechanisms. The Caenorhabditis elegans worm AC5 ortholog, acy‐3 by RNAi, also improved fitness, mitochondrial function, antioxidant defense, and lifespan, attesting to the evolutionary conservation of this pathway. Thus, decreasing sympathetic signaling through loss of AC5 is not only a mechanism to improve exercise performance, but is also a mechanism to improve healthful aging, as exercise also protects against diabetes, obesity, and cardiovascular disease, which all limit healthful aging.

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“…Deletion of NCoR in skeletal muscle resulted in a substantial increase in oxidative metabolism, mitochondrial content, and muscle fiber size. Compared to the wild-type animals, the mutant mice also display an increase in reprogramming to oxidative muscle and better exercise capacity (70).…”

Section: Nr Corepressor (Ncor)mentioning

confidence: 99%

Peroxisome proliferator‐activated receptor‐γ cofactors in neurodegeneration

Katsouri¹,

Blondrath²,

Sastre³

2012

IUBMB Life

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SummaryPeroxisome proliferator-activated receptor-c (PPARc) was initially involved in the regulation of glucose and lipid metabolism, cell differentiation, as well as in the transcriptional control of a wide range of inflammatory genes. However, during the last decade, there has been evidence of the implication of this nuclear receptor in neurodegeneration. Various studies have shown that the administration of PPARc ligands leads to a reduced pathology in many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, and stroke. PPARc cofactors have a critical function in regulating the activity of PPARc. Recent reports have brought to light the role of the PPARc coactivator-1a (PGC-1a) in several neurodegenerative pathologies. However, very little is know about other PPARc cofactors in the brain, such as the receptor-interacting protein 140, as well as the nuclear receptor corepressor, which seems to be required for normal neural development at specific embryonic stages. In this review, we aim to analyze the role of the main regulators of PPARc in the brain and during neurodegeneration.2012 IUBMB IUBMB Life, 64(12): 958-964, 2012

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NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function

Cited by 239 publications

References 68 publications

Fatty acids regulate perilipin5 in muscle by activating PPARδ

Fatty acids regulate perilipin5 in muscle by activating PPARδ

Type 5 adenylyl cyclase disruption leads to enhanced exercise performance

Peroxisome proliferator‐activated receptor‐γ cofactors in neurodegeneration

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