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

International Journal of Obesity volume 31, pages 1660–1670 (2007)Cite this article

Abstract

Objective:

The beneficial metabolic actions of peroxisome proliferator-activated receptor γ (PPARγ) agonism are associated with modifications in adipose tissue metabolism that include a reduction in local glucocorticoid (GC) production by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). This study aimed to assess the contribution of GC attenuation to PPARγ agonism action on gene expression in visceral adipose tissue and global metabolic profile.

Design:

Rats were treated (2 weeks) with the PPARγ agonist rosiglitazone (RSG, 10 mg/kg/day) with concomitant infusion of vehicle (cholesterol implant) or corticosterone (HiCORT, 75 mg/implant/week) to defeat PPARγ-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 (+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. PPARγ 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 HiCORT-induced 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 PPARγ 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 PPARγ agonism are retained under imposed high ambient GC, and are therefore independent from PPARγ effects on 11β-HSD1-mediated GC production.

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Acknowledgements

We acknowledge the invaluable professional assistance of Ms Josée Lalonde and Mr Yves Gélinas. This work was supported by a grant from the Canadian Institutes of Health Research (CIHR) to YD. M Berthiaume was the recipient of a PhD Studentship award from CIHR-Laval University.

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  1. Faculty of Medicine, Laval Hospital Research Center, Laval University, Québec, Québec, Canada

    M Berthiaume, M Laplante & Y Deshaies

  2. Faculty of Medicine, CHUL Medical Research Center, Laval University, Québec, Québec, Canada

    A Tchernof

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Correspondence to Y Deshaies.

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Berthiaume, M., Laplante, M., Tchernof, A. et al. Metabolic action of peroxisome proliferator-activated receptor γ agonism in rats with exogenous hypercorticosteronemia. Int J Obes 31, 1660–1670 (2007). https://doi.org/10.1038/sj.ijo.0803668

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