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
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DOI：
10.1007/s00125-006-0336-y
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发表时间：
2006-10-01
期刊：
影响因子：
8.2
通讯作者：
Deshaies, Y.
中科院分区：
文献类型：
--
作者：
Festuccia, W. T.;Laplante, M.;Deshaies, Y.
目的/假设：本研究的目的是探讨体内过氧化物酶体增殖物激活受体γ（PPAR γ）激活对白色脂肪组织（WAT）脂解和NEFA代谢的影响和作用机制。材料和方法：研究大鼠每天接受15 mg/kg罗格列酮治疗7天;对照大鼠不接受治疗。经过6小时的快速，脂肪分解和脂肪酶的mRNA水平进行了评估，在外植体从各种脂肪depots.Results：罗格列酮显着增加基础和去甲肾上腺素（去甲肾上腺素）刺激的甘油和NEFA从WAT外植体释放，并放大其抑制胰岛素。从经PPAR γ激动剂处理的大鼠中分离的原代脂肪细胞也对每个细胞表达的去甲肾上腺素刺激反应更敏感，排除了外植体中成熟脂肪细胞数量改变的贡献。罗格列酮同时增加皮下和内脏WAT中脂肪甘油三酯脂肪酶（ATGL）和单甘油酯脂肪酶（MGL）的mRNA转录水平，以及皮下WAT中脂肪敏感脂肪酶（HSL）的mRNA转录水平。脂酶表达增加，在12小时内，在体外暴露的幼稚外植体罗格列酮，表明直接转录激活。在平行，慢性罗格列酮在体内治疗降低血浆NEFA和WAT其预期的刺激作用甘油和NEFA回收，并参与NEFA的吸收和保留WAT的基因的表达，这种过程抵消净NEFA export.Conclusions/interpretation：这些研究结果表明，在面对其血浆NEFA降低行动，PPAR γ激动刺激WAT脂解，效果是由脂质保留途径补偿。结果进一步表明，PPAR γ激动通过增加脂解潜力刺激脂解，包括编码脂肪甘油三酯脂肪酶和单甘油酯脂肪酶的基因的表达水平。
Aims/hypothesis: The aim of this study was to investigate the effect and mechanisms of action of in vivo peroxisome proliferator-activated receptor gamma (PPAR gamma) 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 PPAR gamma 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 naive explants to rosiglitazone, suggesting direct transcriptional activation. In parallel, chronic in vivo treatment with rosiglitazone lowered plasma NEFAs and 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, PPAR gamma agonism stimulates WAT lipolysis, an effect that is compensated by lipid-retaining pathways. The results further suggest that PPAR gamma agonism stimulates lipolysis by increasing the lipolytic potential, including the expression levels of the genes encoding adipose triglyceride lipase and monoglyceride lipase.