Actions of PPARgamma agonism on adipose tissue remodeling, insulin sensitivity, and lipemia in absence of glucocorticoids.
Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists improve insulin sensitivity and lipemia partly through enhancing adipose tissue proliferation and capacity for lipid retention. The agonists also reduce local adipose glucocorticoid production, which may in turn contribute to their metabolic actions. This study assessed the effects of a PPARgamma agonist in the absence of glucocorticoids (adrenalectomy, ADX). Intact, ADX, and intact pair-fed (PF) rats were treated with the PPARgamma agonist rosiglitazone (RSG) for 2 wk. RSG increased inguinal (subcutaneous) white (50%) and brown adipose tissue (6-fold) weight but not that of retroperitoneal (visceral) white adipose tissue. ADX but not PF reduced fat accretion in both inguinal and retroperitoneal adipose depots but did not affect brown adipose mass. RSG no longer increased inguinal weight in ADX and PF rats but increased brown adipose mass, albeit less so than in intact rats. RSG increased cell proliferation in white (3-fold) and brown adipose tissue (6-fold), as assessed microscopically and by total DNA, an effect that was attenuated but not abrogated by ADX. RSG reduced the expression of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) in all adipose depots. RSG improved insulin sensitivity (reduction in fasting insulin and homeostasis model assessment of insulin resistance, both -50%) and triacylglycerolemia (-75%) regardless of the glucocorticoid status, these effects being fully additive to those of ADX and PF. In conclusion, RSG partially retained its ability to induce white and brown adipose cell proliferation and brown adipose fat accretion and further improved insulin sensitivity and lipemia in ADX rats, such effects being therefore independent from the PPARgamma-mediated modulation of glucocorticoids.
Berthiaume
Magalie
M
Laval Hospital Research Center, Department of Anatomy and Physiology, School of Medicine, Laval University, Québec, QC, Canada G1K 7P4.
Sell
Henrike
H
Lalonde
Josée
J
Gélinas
Yves
Y
Tchernof
André
A
Richard
Denis
D
Deshaies
Yves
Y
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D000273:Adipose Tissue / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000502:physiology*; D008055:Lipids / Q000097:blood*; D008297:Male; D047495:PPAR gamma / Q000819:agonists*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D001786:Blood Glucose; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D004247:DNA; D042842:11-beta-Hydroxysteroid Dehydrogenases