Berthiaume Magalie, Sell Henrike, Lalonde Josée, Gélinas Yves, Tchernof André, Richard Denis, Deshaies Yves
Laval Hospital Research Center, Department of Anatomy and Physiology, School of Medicine, Laval University, Québec, QC, Canada G1K 7P4.
Am J Physiol Regul Integr Comp Physiol. 2004 Nov;287(5):R1116-23. doi: 10.1152/ajpregu.00339.2004. Epub 2004 Jul 15.
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.
过氧化物酶体增殖物激活受体γ（PPARγ）激动剂部分通过增强脂肪组织增殖和脂质储存能力来改善胰岛素敏感性和血脂异常。这些激动剂还能减少局部脂肪组织中糖皮质激素的生成，这反过来可能有助于其代谢作用。本研究评估了在无糖皮质激素（肾上腺切除术，ADX）情况下PPARγ激动剂的作用。将完整、ADX和完整配对喂养（PF）的大鼠用PPARγ激动剂罗格列酮（RSG）治疗2周。RSG增加了腹股沟（皮下）白色脂肪组织重量（50%）和棕色脂肪组织重量（6倍），但未增加腹膜后（内脏）白色脂肪组织重量。ADX而非PF减少了腹股沟和腹膜后脂肪库中的脂肪堆积，但不影响棕色脂肪量。RSG不再增加ADX和PF大鼠的腹股沟重量，但增加了棕色脂肪量，尽管增加程度低于完整大鼠。通过显微镜检查和总DNA评估，RSG增加了白色脂肪组织（3倍）和棕色脂肪组织（6倍）中的细胞增殖，ADX可减弱但未消除这种作用。RSG降低了所有脂肪库中糖皮质激素激活酶11β-羟基类固醇脱氢酶1（11β-HSD1）的表达。无论糖皮质激素状态如何，RSG均改善了胰岛素敏感性（空腹胰岛素降低和胰岛素抵抗的稳态模型评估降低，均为-50%）和三酰甘油血症（-75%），这些作用与ADX和PF的作用完全相加。总之，RSG部分保留了其诱导白色和棕色脂肪细胞增殖以及棕色脂肪脂肪堆积的能力，并进一步改善了ADX大鼠的胰岛素敏感性和血脂异常，因此这些作用独立于PPARγ介导的糖皮质激素调节。
