Rapid down‐regulation of mitochondrial fat metabolism in human muscle after training cessation is dissociated from changes in insulin sensitivity

Rimbert, Virginie; Vidal, Hubert; Duché, Pascale; Debard, Cyrille; Giraudet, Christophe; Boirie‌, Yves; Chardigny, Jean‐Michel; Morio, Béatrice

doi:10.1016/j.febslet.2009.07.059

Cited by 9 publications

(14 citation statements)

References 34 publications

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“…Given that insulin is known to decrease FA oxidation (Dyck et al 2001;Kelly et al 2008), the rise in several markers of oxidative capacity observed with low RIP140 might be expected to be associated with lower rates of insulin-mediated FA oxidation. In contrast to those expectations, but in line with data obtained by others, our FA oxidation results indicate that a general improvement in oxidative capacity is not necessarily associated with a larger insulin response (Hancock et al 2008;Rimbert et al 2009;Irving et al 2011).…”

Section: Figure 4 Effects Of Rip140 Downregulation On Mrna Expressionsupporting

confidence: 89%

Genetic downregulation of receptor‐interacting protein 140 uncovers the central role of Akt signalling in the regulation of fatty acid oxidation in skeletal muscle cells

Constantinescu¹,

Turcotte²

2012

Experimental Physiology

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New findings r What is the central question of this study?Receptor-interacting protein 140 (RIP140) is a known negative regulator of oxidative capacity. However, the effects of its downregulation on insulin-mediated fatty acid metabolism and of gene expression and Akt-atypical protein kinase C-ζ signalling in skeletal muscle remain incomplete. r What is the main finding and its importance?Our data indicate that downregulation of RIP140 significantly impacts both basal and insulin-mediated activation of Akt and atypical protein kinase C-ζ. This extends the assigned regulatory role of these signalling intermediates during insulin stimulation and suggests that Akt may also be an important regulator of fatty acid oxidation in basal conditions. The role of the nuclear co-repressor receptor-interacting protein 140 (RIP140) in metabolic regulation, gene and protein expression and insulin signalling in skeletal muscle cells remains to be delineated. To study this question, L6 myotubes were treated with or without an RNA interference oligonucleotide sequence to downregulate RIP140 expression and incubated with or without insulin (1 μm). Downregulation of RIP140 increased (P < 0.05) basal palmitate uptake (by 20%) and decreased (P < 0.05) basal palmitate oxidation (by 38%). In control small interfering RNA-treated cells, insulin increased (P < 0.05) glucose (by 31%) and palmitate uptake (by 20%) and decreased (P < 0.05) palmitate oxidation (by 35%). However, in RIP140 small interfering RNA-treated cells, insulin did not affect (P > 0.05) palmitate uptake and increased (P < 0.05) palmitate oxidation (by 79%). In insulin-mediated conditions, downregulation of RIP140 decreased (P < 0.05) Akt Ser473 and atypical protein kinase C-ζ Thr403/410 phosphorylation. As expected, downregulation of RIP140 was accompanied by an increase (P < 0.05) in cytochrome c oxidase subunit 4 isoform 1 and peroxisome proliferator-activated receptor receptor γ coactivator-1α mRNA content. Downregulation of RIP140 increased (P < 0.05) fatty acid transport protein 1 mRNA content and carnitine palmitoyltransferase 1b protein content and decreased (P < 0.05) medium chain acyl-CoA dehydrogenase mRNA content in basal conditions. In insulin-mediated conditions, downregulation of RIP140 increased (P < 0.05) carnitine palmitoyltransferase 1b, fatty acid transport protein 1 and fibroblast growth factor 21 mRNA content and decreased (P < 0.05) medium chain acyl-CoA dehydrogenase mRNA content and plasma membrane fatty acid translocase/cluster of differentiation 36 protein content.

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Section: Figure 4 Effects Of Rip140 Downregulation On Mrna Expressionsupporting

confidence: 89%

Genetic downregulation of receptor‐interacting protein 140 uncovers the central role of Akt signalling in the regulation of fatty acid oxidation in skeletal muscle cells

Constantinescu¹,

Turcotte²

2012

Experimental Physiology

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“…Similarly, athletes that undergo training cessation often experience perturbations in insulin sensitivity and glucose homeostasis (39 -41). These periods of relative insulin resistance are preceded by a reduction in PGC-1␣, carnitine palmitoyltransferase 1b, and citrate synthase gene expression along with reduced mitochondrial lipid oxidation (42). Reduced muscle lipid oxidation in combination with elevated IMCL, i.e.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-activated Receptor γ Coactivator 1α (PGC-1α) Promotes Skeletal Muscle Lipid Refueling in Vivo by Activating de Novo Lipogenesis and the Pentose Phosphate Pathway*

Summermatter

Baum

Santos

et al. 2010

Journal of Biological Chemistry

107

124

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Exercise induces a pleiotropic adaptive response in skeletal muscle, largely through peroxisome proliferator-activated receptor ␥ coactivator 1␣ (PGC-1␣). PGC-1␣ enhances lipid oxidation and thereby provides energy for sustained muscle contraction. Its potential implication in promoting muscle refueling remains unresolved, however. Here, we investigated a possible role of elevated PGC-1␣ levels in skeletal muscle lipogenesis in vivo and the molecular mechanisms that underlie PGC-1␣-mediated de novo lipogenesis. To this end, we studied transgenic mice with physiological overexpression of PGC-1␣ and human muscle biopsies pre-and post-exercise. We demonstrate that PGC-1␣ enhances lipogenesis in skeletal muscle through liver X receptor ␣-dependent activation of the fatty acid synthase (FAS) promoter and by increasing FAS activity. Using chromatin immunoprecipitation, we establish a direct interaction between PGC-1␣ and the liver X receptor-responsive element in the FAS promoter. Moreover, we show for the first time that increased glucose uptake and activation of the pentose phosphate pathway provide substrates for RNA synthesis and cofactors for de novo lipogenesis. Similarly, we observed increased lipogenesis and lipid levels in human muscle biopsies that were obtained post-exercise. Our findings suggest that PGC-1␣ coordinates lipogenesis, intramyocellular lipid accumulation, and substrate oxidation in exercised skeletal muscle in vivo.

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“…The overall quality of the reporting of individual study results, including statistical significance, was poor amongst the manuscripts included in this review. Reporting of estimates of the random variability in the data relating to the main outcome only occurred in nine studies (Kiens et al, ; Mensink et al, ; Arkinstall et al, ; Schenk and Horowitz, ; Helge et al, ; Fu et al, ; Rimbert et al, ; Newsom et al, ; Cheng et al, ), and actual P ‐values were only reported in five manuscripts (Tunstall et al, ; Mensink et al, ; de Bock et al, ; Fu et al, ; Newsom et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…EX+DIET using a high‐fat diet increased expression by 215%, significantly greater than a high‐CHO diet (Cameron‐Smith et al, ). Two studies investigating de‐training both reported no significant change (Rimbert et al, ; Bergouignan et al, ).…”

Section: Resultsmentioning

confidence: 99%

Interactions Between Fatty Acid Transport Proteins, Genes That Encode for Them, and Exercise: A Systematic Review

et al. 2016

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Long-chain fatty acid (LCFA) movement into skeletal muscle involves a highly mediated process in which lipid rafts are utilized in the cellular membrane, involving numerous putative plasma membrane-associated LCFA transport proteins. The process of LCFA uptake and oxidation is of particular metabolic significance both at rest and during light to moderate exercise. A comprehensive systematic search of electronic databases was conducted to investigate whether exercise alters protein and/or gene expression of putative LCFA transport proteins. There were 31 studies meeting all eligibility criteria, of these 13 utilized an acute exercise protocol and 18 examined chronic exercise adaptations. Seventeen involved a study design incorporating an exercise stimulus, while the remaining 14 incorporated a combined exercise and diet stimulus. Divergent data relating to acute exercise, as well as prolonged exercise training (≥3 weeks), on protein content (PC) response was identified for proteins CD36, FABPpm and CAV1. Messenger ribonucleic acid (mRNA) data did not always correspond to functional PC, supporting previous suggestions of a disconnect due to potentially limiting factors post gene expression. The large array of study designs, cohorts, and primary dependent variables within the studies included in the present review elucidate the complexity of the interaction between exercise and LCFA transport proteins. Summary of the results in the present review validate the need for further targeted investigation within this topic, and provide an important information base for such research. J. Cell. Physiol. 231: 1671-1687, 2016. © 2015 Wiley Periodicals, Inc.

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Rapid down‐regulation of mitochondrial fat metabolism in human muscle after training cessation is dissociated from changes in insulin sensitivity

Cited by 9 publications

References 34 publications

Genetic downregulation of receptor‐interacting protein 140 uncovers the central role of Akt signalling in the regulation of fatty acid oxidation in skeletal muscle cells

Genetic downregulation of receptor‐interacting protein 140 uncovers the central role of Akt signalling in the regulation of fatty acid oxidation in skeletal muscle cells

Peroxisome Proliferator-activated Receptor γ Coactivator 1α (PGC-1α) Promotes Skeletal Muscle Lipid Refueling in Vivo by Activating de Novo Lipogenesis and the Pentose Phosphate Pathway*

Interactions Between Fatty Acid Transport Proteins, Genes That Encode for Them, and Exercise: A Systematic Review

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