The Transcriptional Coregulators TIF2 and SRC-1 Regulate Energy Homeostasis by Modulating Mitochondrial Respiration in Skeletal Muscles

Duteil, Delphine; Chambon, Céline; Ali, Faisal; Malivindi, Rocco; Zoll, Joffrey; Kato, Shigeaki; Gény, Bernard; Chambon, Pierre; Metzger, Daniel

doi:10.1016/j.cmet.2010.09.016

Cited by 57 publications

(63 citation statements)

References 46 publications

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“…Present data also suggest the implication of nuclear coactivators such as CREB-regulated transcription coactivator 1, nuclear receptor coactivator MED1 and steroid receptor coactivator (NcoA6) that were simultaneously upregulated in SA juveniles. Experiments in transgenic mice have indeed indicated that these nuclear coreceptors might be involved in muscle energy metabolism [31,32]. Interestingly, MED1 was recently shown to dynamically interact with nuclear T 3 R in the activation of brown-fat-specific thermogenic UCP1 [33] further underlying its role in metabolic adjustments.…”

Section: Discussionmentioning

confidence: 99%

Selective upregulation of lipid metabolism in skeletal muscle of foraging juvenile king penguins: an integrative study

et al. 2012

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The passage from shore to marine life of juvenile penguins represents a major energetic challenge to fuel intense and prolonged demands for thermoregulation and locomotion. Some functional changes developed at this crucial step were investigated by comparing pre-fledging king penguins with sea-acclimatized (SA) juveniles (Aptenodytes patagonicus). Transcriptomic analysis of pectoralis muscle biopsies revealed that most genes encoding proteins involved in lipid transport or catabolism were upregulated, while genes involved in carbohydrate metabolism were mostly downregulated in SA birds. Determination of muscle enzymatic activities showed no changes in enzymes involved in the glycolytic pathway, but increased 3-hydroxyacyl-CoA dehydrogenase, an enzyme of the b-oxidation pathway. The respiratory rates of isolated muscle mitochondria were much higher with a substrate arising from lipid metabolism (palmitoyl-L-carnitine) in SA juveniles than in terrestrial controls, while no difference emerged with a substrate arising from carbohydrate metabolism (pyruvate). In vivo, perfusion of a lipid emulsion induced a fourfold larger thermogenic effect in SA than in control juveniles. The present integrative study shows that fuel selection towards lipid oxidation characterizes penguin acclimatization to marine life. Such acclimatization may involve thyroid hormones through their nuclear beta receptor and nuclear coactivators.

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Section: Discussionmentioning

confidence: 99%

Selective upregulation of lipid metabolism in skeletal muscle of foraging juvenile king penguins: an integrative study

et al. 2012

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“…This may be due to the alterations in BAT or skeletal muscle energetics, where SRC1 competes with SRC2 to regulate genes controlling energy expenditure and uncoupling (13,30). In comparison, the SRC1 ASOs did not alter BAT or muscle expression, and SRC1 ASO treatment did not impact weight gain in either chow-fed or high-fat-fed rats.…”

Section: Discussionmentioning

confidence: 89%

“…SRC1 ASO treatment increased glucose Ϫ/Ϫ mice are prone to diet-induced obesity (13,26,30). To determine whether SRC1 ASO treatment alters weight gain and diet-induced obesity and insulin resistance, rats were treated with control or SRC1 ASO and fed a high-fat diet for 4 wk.…”

Section: Src1 Aso Treatment Increases Peripheral Insulin Sensitivity mentioning

confidence: 99%

Targeting steroid receptor coactivator 1 with antisense oligonucleotides increases insulin-stimulated skeletal muscle glucose uptake in chow-fed and high-fat-fed male rats

Cantley

Vatner²,

Galbo³

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Ϫ/Ϫ mice have decreased hepatic expression of gluconeogenic enzymes and a reduction in the rate of endogenous glucose production (EGP). We sought to determine whether decreasing hepatic and adipose SRC1 expression in normal adult rats would alter glucose homeostasis and insulin action. Regular chow-fed and high-fat-fed male Sprage-Dawley rats were treated with an antisense oligonucleotide (ASO) against SRC1 or a control ASO for 4 wk, followed by metabolic assessments. SRC1 ASO did not alter basal EGP or expression of gluconeogenic enzymes. Instead, SRC1 ASO increased insulin-stimulated whole body glucose disposal by ϳ30%, which was attributable largely to an increase in insulinstimulated muscle glucose uptake. This was associated with an approximately sevenfold increase in adipose expression of lipocalintype prostaglandin D 2 synthase, a previously reported regulator of insulin sensitivity, and an approximately 70% increase in plasma PGD 2 concentration. Muscle insulin signaling, AMPK activation, and tissue perfusion were unchanged. Although GLUT4 content was unchanged, SRC1 ASO increased the cleavage of tether-containing UBX domain for GLUT4, a regulator of GLUT4 translocation. These studies point to a novel role of adipose SRC1 as a regulator of insulin-stimulated muscle glucose uptake. insulin resistance; glucose transporter type 4; skeletal muscle; white adipose tissue GLUCOSE HOMEOSTASIS REQUIRES THE COMPLEX COORDINATION of cellular and molecular pathways in multiple tissues. In many instances, these pathways collate hormonal and metabolic cues to regulate transcription factors that alter the expression of genes encoding key metabolic enzymes. The activity of transcription factors is regulated further by transcriptional coactivators and corepressors. The three members of the p160 steroid coactivator receptor family, the steroid receptor coactivator 1 (SRC1 or NcoA-1), the transcriptional intermediary factor 2 (TIF2, SRC2, GRIP1, or NCOA2), and steroid receptor coactivator 3 (SRC3, p/CIP, AIB1, ACTR, RAC3, or TRAM-1) have all been shown to control energy balance through their interactions with many transcription factors, including nuclear receptors (14,16,18,22). The SRC1 family has also been implicated in many other physiological processes, including reproduction, cancer, and immunity (22,27,42,49,50).A significant body of work has shown that SRC1 is important for the tissue-specific activation of progesterone and estrogen receptors (1,16,42). Additionally, studies using the SRC1 global knockout mice have shown that SRC1 is required for uterine growth and function, prostate development, mammary gland growth and elongation, brain development and function, and metabolism (20,23,24,28,31,49,50,52). SRC1 Ϫ/Ϫ mice also have features of thyroid hormone resistance, with evidence that SRC1 is critical for proper activation of the thyroid hormone receptor-␤ (48). SRC1 Ϫ/Ϫ mice have impairment in brown adipose tissue (BAT) function that makes them prone to weight gain potentially through decreased activation of PGC-1...

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“…It is noteworthy that SRC-2(Ϫ/Ϫ) and SRC-3(Ϫ/Ϫ) mice are protected from diet-induced obesity, whereas SRC-1(Ϫ/Ϫ) mice are more susceptible to weight gain (Picard et al, 2002;Coste et al, 2008). Whole-body SRC-2(Ϫ/Ϫ) and SRC-3(Ϫ/Ϫ) mice, as well as skeletal muscle-specific SRC-2 knockout mice, are characterized by increased energy expenditure and higher body temperatures, responses that seem to be mediated by increased UCP expression and activity in mitochondria of both brown adipose tissue and skeletal muscle (Picard et al, 2002;Coste et al, 2008;Duteil et al, 2010). Normally, SRC-2 and SRC-3 help to maintain optimal efficiency between mitochondrial respiration and ATP synthesis by antagonizing the actions of SRC-1 and/or PGC-1␣, both of which promote UCP expression and thermogenesis.…”

Section: Modifications Of Transcriptional Metabolic Regulatorsmentioning

confidence: 99%

“…Thus, the absence of SRC-2 or SRC-3 leaves SRC-1 unopposed, generating an increase in energy expenditure and activation of mitochondrial biogenesis. In fact, knocking out SRC-2 specifically in muscle is sufficient to protect against high-fat diet-induced obesity and insulin resistance, suggesting that decreasing SRC-2 and/or increasing SRC-1 in skeletal muscle may represent viable strategies for counteracting nutritional overload metabolic disorders (Duteil et al, 2010).…”

Section: Modifications Of Transcriptional Metabolic Regulatorsmentioning

confidence: 99%

Transgenic Mouse Models Resistant to Diet-Induced Metabolic Disease: Is Energy Balance the Key?: Fig. 1.

Gilliam

Neufer

2012

J Pharmacol Exp Ther

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The prevalence and economic burden of obesity and type 2 diabetes is a driving force for the discovery of molecular targets to improve insulin sensitivity and glycemic control. Here, we review several transgenic mouse models that identify promising targets, ranging from proteins involved in the insulin signaling pathway, alterations of genes affecting energy metabolism, and transcriptional metabolic regulators. Despite the diverse endpoints in each model, a common thread that emerges is the necessity for maintenance of energy balance, suggesting pharmacotherapy must target the development of drugs that decrease energy intake, accelerate energy expenditure in a well controlled manner, or augment natural compensatory responses to positive energy balance.

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The Transcriptional Coregulators TIF2 and SRC-1 Regulate Energy Homeostasis by Modulating Mitochondrial Respiration in Skeletal Muscles

Cited by 57 publications

References 46 publications

Selective upregulation of lipid metabolism in skeletal muscle of foraging juvenile king penguins: an integrative study

Selective upregulation of lipid metabolism in skeletal muscle of foraging juvenile king penguins: an integrative study

Targeting steroid receptor coactivator 1 with antisense oligonucleotides increases insulin-stimulated skeletal muscle glucose uptake in chow-fed and high-fat-fed male rats

Transgenic Mouse Models Resistant to Diet-Induced Metabolic Disease: Is Energy Balance the Key?: Fig. 1.

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