Retinoic acids increase expression of GLUT4 in dedifferentiated and hypertrophied cardiac myocytes

Montessuit, Christophe; Papageorgiou, Irène; Campos, Lis; Lerch, René

doi:10.1007/s00395-005-0567-y

Cited by 21 publications

(18 citation statements)

References 39 publications

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“…It was therefore of interest to examine the interaction of ATRA with glucose metabolism in our skeletal muscle cell model. In good concordance with previous observations in cardiac myocytes [48], ATRA exposure increased the mRNA levels of the insulin-regulated glucose transporter GLUT4 in C2C12 skeletal myocytes. However, GLUT4 mRNA levels only indirectly reflect glucose uptake capacity, as this is primarily regulated by transport of GLUT4 to the plasma membrane, and in fact in our hands basal and insulin-stimulated 2-DOG uptake in C2C12 myocytes were unaffected by ATRA treatment.…”

Section: Discussionsupporting

confidence: 80%

Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo

Amengual

García-Carrizo

Arreguín

et al. 2018

Cell Physiol Biochem

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Background/Aims: All-trans retinoic acid (ATRA) has protective effects against obesity and metabolic syndrome. We here aimed to gain further insight into the interaction of ATRA with skeletal muscle metabolism and secretory activity as important players in metabolic health. Methods: Cultured murine C2C12 myocytes were used to study direct effects of ATRA on cellular fatty acid oxidation (FAO) rate (using radioactively-labelled palmitate), glucose uptake (using radioactively-labelled 2-deoxy-D-glucose), triacylglycerol levels (by an enzymatic method), and the expression of genes related to FAO and glucose utilization (by RT-real time PCR). We also studied selected myokine production (using ELISA and immunohistochemistry) in ATRA-treated myocytes and intact mice. Results: Exposure of C2C12 myocytes to ATRA led to increased fatty acid consumption and decreased cellular triacylglycerol levels without affecting glucose uptake, and induced the expression of the myokine irisin at the mRNA and secreted protein level in a dose-response manner. ATRA stimulatory effects on FAO-related genes and the Fndc5 gene (encoding irisin) were reproduced by agonists of peroxisome proliferator-activated receptor β/δ and retinoid X receptors, but not of retinoic acid receptors, and were partially blocked by an AMP-dependent protein kinase inhibitor. Circulating irisin levels were increased by 5-fold in ATRA-treated mice, linked to increased Fndc5 transcription in liver and adipose tissues, rather than skeletal muscle. Immunohistochemistry analysis of FNDC5 suggested that ATRA treatment enhances the release of FNDC5/irisin from skeletal muscle and the liver and its accumulation in interscapular brown and inguinal white adipose depots. Conclusion: These results provide new mechanistic insights on how ATRA globally stimulates FAO and enhances irisin secretion, thereby contributing to leaning effects and improved metabolic status.

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Section: Discussionsupporting

confidence: 80%

Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo

Amengual

García-Carrizo

Arreguín

et al. 2018

Cell Physiol Biochem

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“…Although our previous experiments suggested that the development of insulin resistance in vitro was independent of GLUT4 expression (19), we determined whether changes in GLUT4 expression in response to nuclear receptor agonists could contribute to the improved insulin responsiveness. Similar to published observations (33,39), GLUT4 expression was reduced after 3 d in culture but slightly enhanced in the presence of 9-cis RA or TTNPB (Fig. 7).…”

Section: Expression Of Glucose Transporterssupporting

confidence: 91%

Nuclear Receptor Agonists Improve Insulin Responsiveness in Cultured Cardiomyocytes through Enhanced Signaling and Preserved Cytoskeletal Architecture

2007

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Insulin resistance is the failure of insulin to stimulate the transport of glucose into its target cells. A highly regulatable supply of glucose is important for cardiomyocytes to cope with situations of metabolic stress. We recently observed that isolated adult rat cardiomyocytes become insulin resistant in vitro. Insulin resistance is combated at the whole body level with agonists of the nuclear receptor complex peroxisome proliferator-activated receptor γ (PPARγ)/retinoid X receptor (RXR). We investigated the effects of PPARγ/RXR agonists on the insulin-stimulated glucose transport and on insulin signaling in insulin-resistant adult rat cardiomyocytes. Treatment of cardiomyocytes with ciglitazone, a PPARγ agonist, or 9-cis retinoic acid (RA), a RXR agonist, increased insulin- and metabolic stress-stimulated glucose transport, whereas agonists of PPARα or PPARβ/δ had no effect. Stimulation of glucose transport in response to insulin requires the phosphorylation of the signaling intermediate Akt on the residues Thr308 and Ser473 and, downstream of Akt, AS160 on several Thr and Ser residues. Phosphorylation of Akt and AS160 in response to insulin was lower in insulin-resistant cardiomyocytes. However, treatment with 9-cis RA markedly increased phosphorylation of both proteins. Treatment with 9-cis RA also led to better preservation of microtubules in cultured cardiomyocytes. Disruption of microtubules in insulin-responsive cardiomyocytes abolished insulin-stimulated glucose transport and reduced phosphorylation of AS160 but not Akt. Metabolic stress-stimulated glucose transport also involved AS160 phosphorylation in a microtubule-dependent manner. Thus, the stimulation of glucose uptake in response to insulin or metabolic stress is dependent in cardiomyocytes on the presence of intact microtubules.

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“…Adult rat cardiac myocytes were isolated as described previously (39) and cultured in M199 medium (Sigma-Aldrich) supplemented with 20 mM creatine, 100 M cytosine-␤-D-arabinofuranoside, 20% FCS, and 10 Ϫ7 M 9-cis retinoic acid to improve cardiac myocyte differentiation (38) and prevent transient insulin resistance (39). All additions to this basal medium were present at the time of plating (day 0) and for the entire length of the culture.…”

Section: Animalsmentioning

confidence: 99%

Differential regulation of stimulated glucose transport by free fatty acids and PPARα or -δ agonists in cardiac myocytes

Asrih

Lerch

Papageorgiou

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Stimulation of glucose transport in response to insulin or metabolic stress is an important determinant of cardiac myocyte function and survival, particularly during ischemia-reperfusion episodes. The impact of dyslipidemia and its consequence PPAR activation on stimulated glucose transport in cardiac myocytes remains unknown. Isolated adult rat cardiac myocytes were chronically exposed to free fatty acids (FFA) or PPAR agonists. Insulin- (ISGT) and oligomycin-stimulated glucose transport (OSGT) and related cell signaling were analyzed. Exposure of cardiac myocytes to FFA reduced both ISGT and OSGT. Exposure to either PPARα or PPARδ agonists, but not to a PPARγ agonist, reduced ISGT but not OSGT and increased fatty acid oxidation (FAO). The reduction in ISGT was associated with impaired insulin signaling and, in the case of PPAR stimulation, overexpression of SOCS-3, a protein known to hinder proximal insulin signaling. In contrast, the reduction of OSGT could not be explained by a reduced activity of the cellular energy-sensing system, as assessed from the maintained phosphorylation state of AMPK. Inhibition of FAO at the level of mitochondrial acylcarnitine uptake restored OSGT but not ISGT. Seemingly paradoxically, further stimulation of FAO with PPARα or PPARδ agonists also restored OSGT but not ISGT. Together, these results suggest that inhibition of OSGT occurs downstream of energy gauging and is caused by some intermediate(s) of fatty acid oxidation, which does not appear to be acylcarnitines. The results indicate that the mechanisms underlying FFA-mediated inhibition of ISGT and OSGT differ remarkably.

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Retinoic acids increase expression of GLUT4 in dedifferentiated and hypertrophied cardiac myocytes

Cited by 21 publications

References 39 publications

Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo

Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo

Nuclear Receptor Agonists Improve Insulin Responsiveness in Cultured Cardiomyocytes through Enhanced Signaling and Preserved Cytoskeletal Architecture

Differential regulation of stimulated glucose transport by free fatty acids and PPARα or -δ agonists in cardiac myocytes

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