Exercise increases the binding of <scp>MEF</scp>2A to the Cpt1b promoter in mouse skeletal muscle

Yuan, Hairui; Niu, Yanmei; Liu, X.; Li, Fu

doi:10.1111/apha.12395

Cited by 29 publications

(29 citation statements)

References 27 publications

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“…Exercise benefits at the molecular level are linked, in part, to transcriptional activation myocyte-specific enhancer factor (MEF) 2A in coordination with PPAR-γ, PPARGC1a, and acetylation of GLUT4 in the skeletal muscle [53]. It has been recently shown that exercise increases the binding of MEF2A to the Cpt1b promoter in the mouse skeletal muscle and this requires repression of MEF2A-binding partners such as HDAC5 and HDAC3 [54]. Interestingly, a short-term intensive practice of mindfulness meditation has been demonstrated to rapidly decrease histone deacetylases (more strikingly HDAC3) and inflammatory gene expression [55] implying that appropriate lifestyle modifications may offer metabolic benefits operating through epigenetic mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Augmentation of histone deacetylase 3 (HDAC3) epigenetic signature at the interface of proinflammation and insulin resistance in patients with type 2 diabetes

et al. 2016

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BackgroundA role of proinflammation has been implicated in the pathogenesis of diabetes, but the up-stream regulatory signals and molecular signatures are poorly understood. While histone modifications such as changes in histone deacetylase (HDAC) are emerging as novel epigenetic biomarkers, there is lack of studies to demonstrate their clinical relevance in diabetes. Therefore, we investigated the extent of HDAC machinery and inflammatory signals in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes mellitus (T2DM) compared to control subjects.Results HDAC3 activity was significantly (p < 0.05) increased in patients with T2DM compared to control subjects. While subtypes of HDACs were differentially expressed at their transcriptional levels in patients with type 2 diabetes, the most prominent observation is the significantly (p < 0.05) elevated messenger RNA (mRNA) levels of HDAC3. Expression levels of Sirt1 which represents the class III HDAC were decreased significantly in T2DM (p < 0.05). Plasma levels of both TNF-α and IL-6 were significantly higher (p < 0.05) in patients with type 2 diabetes compared to control subjects. Among the proinflammatory mediators, the mRNA expression of MCP-1, IL1-β, NFκB, TLR2, and TLR4 were also significantly (p < 0.05) increased in T2DM. Transcriptional levels of DBC1 (deleted in breast cancer 1, which is a negative regulator of HDAC3) were seen significantly reduced in PBMCs from T2DM. Interestingly, HDAC3 activity/HDAC3 mRNA levels positively correlated to proinflammation, poor glycemic control, and insulin resistance.ConclusionsStriking message from this study is that while looking for anti-inflammatory strategies and drugs with novel mode of action for T2DM, discovering and designing specific inhibitors targeted to HDAC3 appears promising.

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Section: Discussionmentioning

confidence: 99%

Augmentation of histone deacetylase 3 (HDAC3) epigenetic signature at the interface of proinflammation and insulin resistance in patients with type 2 diabetes

et al. 2016

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“…Activation of AMPK leads to phosphorylation and nuclear exclusion of class IIa HDACs, which relieves repression of myocyte enhancer factor‐2 (MEF2), a transcription factor that regulating the transcription of PGC‐1α and GLUT4 . Our previous study showed that CPT1b expression was also regulated by HDAC5/MEF2A interaction . In the present study, we found that overexpression or knockdown of HSPB1 altered the phosphorylation of HDAC5 at Ser259/498 and HDAC4 at Ser246.…”

Section: Discussionmentioning

confidence: 48%

AMP‐activated protein kinase‐mediated expression of heat shock protein beta 1 enhanced insulin sensitivity in the skeletal muscle

et al. 2016

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Activation of AMP-activated protein kinase (AMPK) has been viewed as an important target for the treatment of insulin resistance. Here, by proteomic analysis, we found that expression of heat shock protein beta-1 (HSPB1) was induced by the AMP analog 5-aminoimidazole-4-carboxamide 1-b-D-ribofuranoside in palmitate-induced insulin-resistant cells. Overexpression of AMPKa2, or activation of AMPKa via acute/chronic exercise training, increased HSPB1 expression in the skeletal muscle. In AMPKa2 À/À mice, HSPB1 expression was downregulated in the quadriceps muscles. Exercise did not increase HSPB1 expression in AMPKa2 À/À mice. Moreover, overexpression of HSPB1 enhanced insulin sensitivity in palmitate-induced insulinresistant cells and restored metabolic phenotypes associated with defective AMPK. Finally, HSPB1 was required for AMPK-mediated activation of the class IIa histone deacetylases and glucose uptake in the skeletal muscle. Our results demonstrate that AMPK-mediated HSPB1 expression enhanced insulin sensitivity in the skeletal muscle.

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“…), and these changes were shown to be regulated in part by myocyte‐specific enhancer factor (Yuan et al. ). After 5 weeks of hypobaric hypoxia (simulated 4000 m), muscle CPT‐1 activity was shown to be markedly decreased in rat quadriceps muscles, whereas these activity levels reached those of normoxic sedentary controls after exercise training under hypoxia, which indicated that exercise training restored muscle CPT activity in the hypoxic environment (Galbès et al.…”

Section: Discussionmentioning

confidence: 99%

“…Aerobic exercise training for 6 weeks markedly increased CPT-1 mRNA and protein levels in mice skeletal muscle (Niu et al 2010), and these changes were shown to be regulated in part by myocyte-specific enhancer factor (Yuan et al 2014). After 5 weeks of hypobaric hypoxia (simulated 4000 m), muscle CPT-1 activity was shown to be markedly decreased in rat quadriceps muscles, whereas *, significantly different from the Cnt group at P < 0.05 using a one-way ANOVA followed by Tukey's post hoc test and 95% confidential interval did not contain the parameter value specified in the null hypothesis.…”

Section: Chronic Response Of Exercise Training With Intermittent Hypomentioning

confidence: 93%

Short-duration intermittent hypoxia enhances endurance capacity by improving muscle fatty acid metabolism in mice

Suzuki

2016

Physiol Rep

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This study was designed to (1) investigate the effects of acute short‐duration intermittent hypoxia on muscle mRNA and microRNA expression levels; and (2) clarify the mechanisms by which short‐duration intermittent hypoxia improves endurance capacity. Experiment‐1: Male mice were subjected to either acute 1‐h hypoxia (12% O2), acute short‐duration intermittent hypoxia (12% O2 for 15 min, room air for 10 min, 4 times, Int‐Hypo), or acute endurance exercise (Ex). The expression of vascular endothelial growth factor‐A mRNA was significantly greater than the control at 0 h post Ex and 6 h post Int‐Hypo in the deep red region of the gastrocnemius muscle. miR‐16 expression levels were significantly lower at 6 and 10 h post Int‐Hypo. Peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α) mRNA levels were significantly greater than the control at 3 h post Ex and 6 h post Int‐Hypo. miR‐23a expression levels were lower than the control at 6–24 h post Int‐Hypo. Experiment‐2: Mice were subjected to normoxic exercise training with or without intermittent hypoxia for 3 weeks. Increases in maximal exercise capacity were significantly greater by training with short‐duration intermittent hypoxia (IntTr) than without hypoxia. Both 3‐Hydroxyacyl‐CoA‐dehydrogenase and total carnitine palmitoyl transferase activities were significantly enhanced in IntTr. Peroxisome proliferator‐activated receptor delta and PGC‐1α mRNA levels were both significantly greater in IntTr than in the sedentary controls. These results suggest that exercise training under normoxic conditions with exposure to short‐duration intermittent hypoxia represents a beneficial strategy for increasing endurance performance by enhancing fatty acid metabolism in skeletal muscle.

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Exercise increases the binding of MEF2A to the Cpt1b promoter in mouse skeletal muscle

Abstract: Our results indicated that exercise-induced CPT1b expression was at least in part mediated by HDAC5/MEF2A interaction.

Cited by 29 publications

References 27 publications

Augmentation of histone deacetylase 3 (HDAC3) epigenetic signature at the interface of proinflammation and insulin resistance in patients with type 2 diabetes

Augmentation of histone deacetylase 3 (HDAC3) epigenetic signature at the interface of proinflammation and insulin resistance in patients with type 2 diabetes

AMP‐activated protein kinase‐mediated expression of heat shock protein beta 1 enhanced insulin sensitivity in the skeletal muscle

Short-duration intermittent hypoxia enhances endurance capacity by improving muscle fatty acid metabolism in mice

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