Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity

Chu, Yajing; Rosso, Leonardo Gómez; Huang, Ping; Wang, Zhichao; Xu, Yichi; Xiao, Yao; Bao, Menghan; Yan, Jun; Song, Haiyun; Wang, Gang

doi:10.1038/cr.2014.120

Cited by 46 publications

(42 citation statements)

References 70 publications

(90 reference statements)

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“…Yet another study demonstrated that MED15 is required for SREBP-1 activation of lipogenic target genes in nematodes (Yang et al, 2006). MED1, MED14, and MED23 are required for adipocyte development, and are ultimately involved in lipid metabolism as well (Chu et al, 2014; Zhang et al, 2013). Interestingly, the nuclear corepressor RIP140 interacts with CDK8 to regulate gene expression during fibroblast-adipocyte differentiation (Nautiyal et al, 2013).…”

Section: Metabolic Functions Of Mediator Components In Musclementioning

confidence: 99%

Muscle as a “Mediator” of Systemic Metabolism

2015

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Skeletal and cardiac muscles play key roles in the regulation of systemic energy homeostasis and display remarkable plasticity in their metabolic responses to caloric availability and physical activity. In this Perspective we discuss recent studies highlighting transcriptional mechanisms that govern systemic metabolism by striated muscles. We focus on the participation of the Mediator complex in this process, and suggest that tissue-specific regulation of Mediator subunits impacts metabolic homeostasis.

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Section: Metabolic Functions Of Mediator Components In Musclementioning

confidence: 99%

Muscle as a “Mediator” of Systemic Metabolism

2015

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“…Numerous members of the NR family are sensors of metabolic status that respond to dietary signals and metabolites, and are responsible for metabolic adaptation at the cell, organ, and whole organismal level (Fig. 3) (Ito and Roeder 2001; Ge et al 2002, 2008; Huss 2004; Smith and Muscat 2005; Yang et al 2006; Wang et al 2009; Chen et al 2010; Grontved et al 2010; Krebs et al 2011; Rana et al 2011; Grueter et al 2012; Zhao et al 2012; Baskin et al 2014; Chu et al 2014; Jia et al 2014, 2016; Lee et al 2014; Amoasii et al 2016). Mediator complex subunits have been shown to interact strongly with numerous NRs in a ligand-dependent manner, and to interact with transcription factors to regulate a variety of metabolic processes.…”

Section: The Mediator Complexmentioning

confidence: 99%

Control of Muscle Metabolism by the Mediator Complex

Amoasii

Olson

Bassel‐Duby

2017

Cold Spring Harb Perspect Med

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Exercise represents an energetic challenge to whole-body homeostasis. In skeletal muscle, exercise activates a variety of signaling pathways that culminate in the nucleus to regulate genes involved in metabolism and contractility; however, much remains to be learned about the transcriptional effectors of exercise. Mediator is a multiprotein complex that links signal-dependent transcription factors and other transcriptional regulators with the basal transcriptional machinery, thereby serving as a transcriptional “hub.” In this article, we discuss recent studies highlighting the role of Mediator subunits in metabolic regulation and glucose metabolism, as well as exercise responsiveness. Elucidation of the roles of Mediator subunits in metabolic control has revealed new mechanisms and molecular targets for the modulation of metabolism and metabolic disorders.

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“…For example, MED1, a core Mediator subunit, binds to nuclear receptors, and its deletion in skeletal muscle enhances metabolism (Chen et al 2010;Jia et al 2014). Additional components of the Mediator complex are involved in fatty acid, cholesterol, and lipid homeostasis (Yang et al 2006;Zhao et al 2012;Tsai et al 2013;Chu et al 2014). We reported that cardiac overexpression of MED13 increases energy consumption and confers a lean phenotype in mice (Grueter et al 2012;Baskin et al 2014).…”

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confidence: 95%

A MED13-dependent skeletal muscle gene program controls systemic glucose homeostasis and hepatic metabolism

et al. 2016

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The Mediator complex governs gene expression by linking upstream signaling pathways with the basal transcriptional machinery. However, how individual Mediator subunits may function in different tissues remains to be investigated. Through skeletal muscle-specific deletion of the Mediator subunit MED13 in mice, we discovered a gene regulatory mechanism by which skeletal muscle modulates the response of the liver to a high-fat diet. Skeletal muscle-specific deletion of MED13 in mice conferred resistance to hepatic steatosis by activating a metabolic gene program that enhances muscle glucose uptake and storage as glycogen. The consequent insulin-sensitizing effect within skeletal muscle lowered systemic glucose and insulin levels independently of weight gain and adiposity and prevented hepatic lipid accumulation. MED13 suppressed the expression of genes involved in glucose uptake and metabolism in skeletal muscle by inhibiting the nuclear receptor NURR1 and the MEF2 transcription factor. These findings reveal a fundamental molecular mechanism for the governance of glucose metabolism and the control of hepatic lipid accumulation by skeletal muscle. Intriguingly, MED13 exerts opposing metabolic actions in skeletal muscle and the heart, highlighting the customized, tissue-specific functions of the Mediator complex.

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Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity

Cited by 46 publications

References 70 publications

Muscle as a “Mediator” of Systemic Metabolism

Muscle as a “Mediator” of Systemic Metabolism

Control of Muscle Metabolism by the Mediator Complex

A MED13-dependent skeletal muscle gene program controls systemic glucose homeostasis and hepatic metabolism

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