Peroxisome Proliferator-Activated Receptor (PPAR) γ and Retinoid X Receptor (RXR) agonists have complementary effects on glucose and lipid metabolism in human skeletal muscle

Soo, Bong; Ciaraldi, Theodore P.; Carter, L.; Nikoulina, Svetlana E.; Mudaliar, Sunder; Mukherjee, Ranjan; Paterniti, James R.; Henry, Robert R.

doi:10.1007/s001250051642

Cited by 105 publications

(90 citation statements)

References 39 publications

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“…Under the same circumstances where FFA uptake was upregulated by thiazolidinedione treatment, ␤-oxidation of palmitate was also increased by all three agents (Fig. 2C) in both nondiabetic and diabetic muscle cells, in confirmation of previous results (15).…”

Section: Resultssupporting

confidence: 90%

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Thiazolidinediones upregulate impaired fatty acid uptake in skeletal muscle of type 2 diabetic subjects

Wilmsen

Ciaraldi

Carter

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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We examined the regulation of free fatty acid (FFA, palmitate) uptake into skeletal muscle cells of nondiabetic and type 2 diabetic subjects. Palmitate uptake included a protein-mediated component that was inhibited by phloretin. The protein-mediated component of uptake in muscle cells from type 2 diabetic subjects (78 ± 13 nmol · mg protein-1 · min-1) was reduced compared with that in nondiabetic muscle (150 ± 17, P < 0.01). Acute insulin exposure caused a modest (16 ± 5%, P < 0.025) but significant increase in protein-mediated uptake in nondiabetic muscle. There was no significant insulin effect in diabetic muscle (+19 ± 19%, P = not significant). Chronic (4 day) treatment with a series of thiazolidinediones, troglitazone (Tgz), rosiglitazone (Rgz), and pioglitazone (Pio) increased FFA uptake. Only the phloretin-inhibitable component was increased by treatment, which normalized this activity in diabetic muscle cells. Under the same conditions, FFA oxidation was also increased by thiazolidinedione treatment. Increases in FFA uptake and oxidation were associated with upregulation of fatty acid translocase (FAT/CD36) expression. FAT/CD36 protein was increased by Tgz (90 ± 22% over control), Rgz (146 ± 42%), and Pio (111 ± 37%, P < 0.05 for all 3) treatment. Tgz treatment had no effect on fatty acid transporter protein-1 and membrane-associated plasmalemmal fatty acid-binding protein mRNA expression. We conclude that FFA uptake into cultured muscle cells is, in part, protein mediated and acutely insulin responsive. The basal activity of FFA uptake is impaired in type 2 diabetes. In addition, chronic thiazolidinedione treatment increased FFA uptake and oxidation into cultured human skeletal muscle cells in concert with upregulation of FAT/CD36 expression. Increased FFA uptake and oxidation may contribute to lower circulating FFA levels and reduced insulin resistance in skeletal muscle of individuals with type 2 diabetes following thiazolidinedione treatment.

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Section: Resultssupporting

confidence: 90%

“…2), resulting in an increase in overall FFA disposal. Studies indicate that Tgz acts to increase the mitochondrial component of palmitate oxidation (15). We therefore hypothesize that thiazolidinediones are involved in directing FFA to the mitochondria by upregulating FFA uptake mediators.…”

Section: Discussionmentioning

confidence: 92%

Thiazolidinediones upregulate impaired fatty acid uptake in skeletal muscle of type 2 diabetic subjects

Wilmsen

Ciaraldi

Carter

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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“…TZDs increase the expression of insulin receptor substrate (IRS)-1 (10), IRS-2 (11), the p85 subunit of phosphatidylinositol 3-kinase (12), and the Cbl-associated protein (13,14). These results are in line with the fact that TZDs increase insulin-stimulated glucose uptake in L6 myotubes (15) and in cultured human skeletal muscle cells (16,17). In addition to the insulin-sensitizing effects in peripheral tissues, PPAR-␥ is known to increase the glucose-sensing ability of pancreatic ␤-cells.…”

supporting

confidence: 77%

Role of Peroxisome Proliferator-Activated Receptor-γ in the Glucose-Sensing Apparatus of Liver and β-Cells

2004

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“…As additive or synergistic effects on glucose, lipid metabolism and gene activation have been described for RXR and PPAR␥ ligands (67)(68)(69)(70)(71)(72)(73), experiments of coincubation of 9cRA with ROSI were performed (Fig. 4).…”

Section: Discussionmentioning

confidence: 99%

9-cis-Retinoic Acid (9cRA), a Retinoid X Receptor (RXR) Ligand, Exerts Immunosuppressive Effects on Dendritic Cells by RXR-Dependent Activation: Inhibition of Peroxisome Proliferator-Activated Receptor γ Blocks Some of the 9cRA Activities, and Precludes Them to Mature Phenotype Development

Zapata-Gonzalez

Rueda

Pétriz

et al. 2007

The Journal of Immunology

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At nanomolar range, 9-cis-retinoic acid (9cRA) was able to interfere in the normal differentiation process from human monocyte to immature dendritic cell (DC) and produced a switch in mature DCs to a less stimulatory mode than untreated cells. 9cRA-treated mature DCs secreted high levels of IL-10 with an IL-12 reduced production. The phenotypic alterations unleashed by 9cRA were similar but not identical to other specific retinoid X receptor (RXR) agonists and to those already reported for rosiglitazone, a PPARγ activator, on DCs. The simultaneous addition of 9cRA and rosiglitazone on DCs displayed additive effects. Moreover, addition to cultures of GW9662, a specific inhibitor of PPARγ, or the RXR pan-antagonist HX603, blocked these changes. All these results suggest an activation of PPARγ-RXR and other RXR containing dimers by 9cRA in DCs. Finally, both GW9662 and HX603 by themselves altered the maturation process unleashed by TNFα, poly(I:C) or LPS on human DCs further suggesting that the heterodimer PPARγ-RXR must fulfill a significant role in the physiological maturation process of these cells in addition to the repressing effects reported till now for this nuclear receptor.

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Peroxisome Proliferator-Activated Receptor (PPAR) γ and Retinoid X Receptor (RXR) agonists have complementary effects on glucose and lipid metabolism in human skeletal muscle

Cited by 105 publications

References 39 publications

Thiazolidinediones upregulate impaired fatty acid uptake in skeletal muscle of type 2 diabetic subjects

Thiazolidinediones upregulate impaired fatty acid uptake in skeletal muscle of type 2 diabetic subjects

Role of Peroxisome Proliferator-Activated Receptor-γ in the Glucose-Sensing Apparatus of Liver and β-Cells

9-cis-Retinoic Acid (9cRA), a Retinoid X Receptor (RXR) Ligand, Exerts Immunosuppressive Effects on Dendritic Cells by RXR-Dependent Activation: Inhibition of Peroxisome Proliferator-Activated Receptor γ Blocks Some of the 9cRA Activities, and Precludes Them to Mature Phenotype Development

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