PPARγ<scp>AND</scp>G<scp>LUCOSE</scp>H<scp>OMEOSTASIS</scp>

Picard, Frédéric; Auwerx, Johan

doi:10.1146/annurev.nutr.22.010402.102808

Cited by 387 publications

(243 citation statements)

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“…The study confirmed the well-established actions of rosiglitazone on morphometric variables, indices of insulin sensitivity and lipidaemia [18][19][20][21]. Several lines of evidence suggest that thiazolidinediones exert their beneficial effects on whole-body insulin sensitivity partly by reducing circulating NEFAs and the consequent exposure of nonadipose tissues to the deleterious effects of NEFA metabolites on insulin signal transduction [2].…”

Section: Discussionsupporting

confidence: 80%

PPARγ agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control

et al. 2006

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Aims/hypothesis The aim of this study was to investigate the effect and mechanisms of action of in vivo peroxisome proliferator-activated receptor γ (PPARγ) activation on white adipose tissue (WAT) lipolysis and NEFA metabolism. Materials and methods Study rats were treated for 7 days with 15 mg/kg of rosiglitazone per day; control rats were not treated. After a 6-h fast, lipolysis and levels of mRNA for lipases were assessed in explants from various adipose depots. Results Rosiglitazone markedly increased basal and noradrenaline (norepinephrine)-stimulated glycerol and NEFA release from WAT explants, and amplified their inhibition by insulin. Primary adipocytes isolated from PPARγ agonist-treated rats were also more responsive to noradrenaline stimulation expressed per cell, ruling out a contribution of an altered number of mature adipocytes in explants. Rosiglitazone concomitantly increased levels of mRNA transcripts for adipose triglyceride lipase (ATGL) and monoglyceride lipase (MGL) in subcutaneous and visceral WAT, and mRNA for hormone-sensitive lipase (HSL) in subcutaneous WAT. Lipase expression increased within 12 h of in vitro exposure of naïve explants to rosiglitazone, suggesting direct transcriptional activation. In parallel, chronic in vivo treatment with rosiglitazone lowered plasma NEFAs and exerted in WAT its expected stimulatory action on glycerol and NEFA recycling, and on the expression of genes involved in NEFA uptake and retention by WAT, such processes counteracting net NEFA export. Conclusions/interpretation These findings demonstrate that, in the face of its plasma NEFA-lowering action, PPARγ agonism stimulates WAT lipolysis, an effect that is compensated by lipid-retaining pathways. The results further suggest that PPARγ agonism stimulates lipolysis by increasing the lipolytic potential, including the expression levels of the genes encoding adipose triglyceride lipase and monoglyceride lipase.

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Section: Discussionsupporting

confidence: 80%

PPARγ agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control

et al. 2006

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“…Vitamin E regulates several genes; for example, it upregulates the expression of PPARG, the gene for peroxisome proliferator activated receptor γ (PPARγ) [20]. PPARγ is a nuclear receptor the stimulation of which improves glucose tolerance and insulin sensitivity in type 2 diabetes mellitus patients and in animal models of insulin resistance [21]. Vitamin E possesses a structural similarity to glucose-lowering agents such as thiazolidinediones, which are agonists for PPARγ.…”

Section: Discussionmentioning

confidence: 99%

Effect of α-tocopherol and β-carotene supplementation on the incidence of type 2 diabetes

Kataja-Tuomola¹,

Sundell²,

Männistö³

et al. 2007

Diabetologia

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Aims/hypothesis Type 2 diabetes is associated with reduced antioxidant defence. Only a few human studies have investigated the role of antioxidants in the pathogenesis of diabetes. This study aimed to examine whether α-tocopherol or β-carotene affected the occurrence of type 2 diabetes. Methods In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, controlled trial, 29,133 male smokers aged 50-69 years were randomised to receive either α-tocopherol (50 mg/day) or β-carotene (20 mg/day) or both agents or placebo daily for 5-8 years (median 6.1 years). Baseline serum samples were analysed for α-tocopherol and β-carotene using HPLC. Cases of diabetes were identified from a nationwide Finnish registry of patients receiving drug reimbursement for diabetes. Of 27,379 men without diabetes at baseline, 705 men were diagnosed with diabetes during the follow-up of up to 12.5 years. Results Baseline serum levels of α-tocopherol and β-carotene were not associated with the risk of diabetes in the placebo group: the relative risk (RR) between the highest and lowest quintiles of α-tocopherol was 1.59 (95% CI 0.89-2.84) and that for β-carotene was 0.66 (95% CI 0.40-1.10). Neither supplementation significantly affected the incidence of diabetes: the RR was 0.92 (95% CI 0.79-1.07) for participants receiving α-tocopherol compared with nonrecipients and 0.99 (95% CI 0.85-1.15) for participants receiving β-carotene compared with non-recipients. Conclusions/interpretation Neither α-tocopherol nor β-carotene supplementation prevented type 2 diabetes in male smokers. Serum levels of α-tocopherol and β-carotene were not associated with the risk of type 2 diabetes.ClinicalTrials.gov ID no. NCT00342992

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“…With respect to PPARg agonism, its proliferative and fat accreting actions are well established. 1,2,33 In rodent models, there exists a dose-dependent depot specificity of action of PPARg agonists on adipose cell proliferation and fat accretion, and low doses such as that used here increase both subcutaneous and visceral fat cellularity and mass. 9,11,12,25 Because our previous study in adrenalectomized rats suggested that, in vivo, GC may facilitate PPARg-mediated proliferative and lipid storage capacity, 25 it was deemed of interest to assess whether maintenance of high levels of CORT would impact the latter.…”

Section: Pparc In Rats With Hypercorticosteronemia M Berthiaume Et Almentioning

confidence: 99%

“…1,2 Thiazolidinediones such as rosiglitazone and pioglitazone are synthetic PPARg agonists that are used clinically for treatment of type 2 diabetes. 3 In addition to positive alterations in the adipokine profile that include increased expression of the insulin-sensitizing adiponectin, 4,5 the beneficial effects of PPARg agonists on insulin sensitivity and on the lipid profile appear to be partly attributable to lipid retention in adipose tissue and consequent reduction in lipid exposure of nonadipose tissues.…”

Section: Introductionmentioning

confidence: 99%

Metabolic action of peroxisome proliferator-activated receptor γ agonism in rats with exogenous hypercorticosteronemia

et al. 2007

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Objective: The beneficial metabolic actions of peroxisome proliferator-activated receptor g (PPARg) agonism are associated with modifications in adipose tissue metabolism that include a reduction in local glucocorticoid (GC) production by 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1). This study aimed to assess the contribution of GC attenuation to PPARg agonism action on gene expression in visceral adipose tissue and global metabolic profile. Design: Rats were treated (2 weeks) with the PPARg agonist rosiglitazone (RSG, 10 mg/kg/day) with concomitant infusion of vehicle (cholesterol implant) or corticosterone (HiCORT, 75 mg/implant/week) to defeat PPARg-mediated GC attenuation. Measurements: mRNA levels of enzymes involved in lipid uptake (and lipoprotein lipase activity), storage, lipolysis, recycling, and oxidation in retroperitoneal white adipose tissue (RWAT). Serum glucose, insulin and lipids, and lipid content of oxidative tissues. Results: Whereas HiCORT did not alter RWAT mass, RSG increased the latter ( þ 33%) independently of the corticosterone status. Both HiCORT and RSG increased lipoprotein lipase activity, the mRNA levels of the de novo lipogenesis enzyme fatty acid synthase, and that of the fatty acid retention-promoting enzyme acyl-CoA synthase 1, albeit in a nonadditive fashion. Expression level of the lipolysis enzyme adipose triglyceride lipase was increased additively by HiCORT and RSG. PPARg agonism increased mRNA of the fatty acid recycling enzymes glycerol kinase and cytosolic phosphoenolpyruvate carboxykinase and those of the fatty acid oxidation enzymes muscle-type carnitine palmitoyltransferase 1 and acyl-CoA oxidase, whereas HiCORT remained without effect. HiCORT resulted in liver steatosis and hyperinsulinemia, which were abrogated by RSG, whereas the HiCORTinduced elevation in serum nonesterified fatty acid levels was only partially prevented. The hypotriglyceridemic action of RSG was maintained in HiCORT rats. Conclusion: The GC and PPARg pathways exert both congruent and opposite actions on specific aspects of adipose tissue metabolism. Both the modulation of adipose gene expression and the beneficial global metabolic actions of PPARg agonism are retained under imposed high ambient GC, and are therefore independent from PPARg effects on 11b-HSD1-mediated GC production.

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PPARγANDGLUCOSEHOMEOSTASIS

Cited by 387 publications

References 230 publications

PPARγ agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control

PPARγ agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control

Effect of α-tocopherol and β-carotene supplementation on the incidence of type 2 diabetes

Metabolic action of peroxisome proliferator-activated receptor γ agonism in rats with exogenous hypercorticosteronemia

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