Additive action of 11β-HSD1 inhibition and PPAR-γ agonism on hepatic steatosis and triglyceridemia in diet-induced obese rats
Additive action of 11β-HSD1 inhibition and PPAR-γ agonism on hepatic steatosis and triglyceridemia in diet-induced obese rats
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DOI：
10.1038/ijo.2009.33
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发表时间：
2009-05-01
影响因子：
4.9
通讯作者：
Deshaies, Y.
中科院分区：
文献类型：
--
作者：
Berthiaume, M.;Laplante, M.;Deshaies, Y.
11β-羟基类固醇脱氢酶(11β-HSD1)抑制和过氧化体增殖物激活受体-γ(PPAR-γ)激动剂均通过部分不同的机制降低啮齿动物肝脏和血脂。这项研究旨在评估它们在饮食诱导的脂肪变性模型中对肝脏和血脂的作用的可加性。以肥胖饲料喂养大鼠，给予11β-HSD1抑制剂(化合物A，3 mg kg(-1)day(-1))和罗格列酮(RSG，5 mg kg(-1)day(-1))或两者联合治疗6周。化合物A和RSG可减少肝脏脂肪变性和甘油三酯血症，当联合服用时，其作用是相加的。11β-HSD1抑制剂对血清脂联素无影响，但增加肝脂联素受体2型(ADPO-R2)的mRNA水平。相反，RSG增加了血清脂联素，这可能是其抗脂肪变性作用的中介，但本身对ADIPO-R2的表达没有影响。两种化合物均有提高脂肪酸氧化代表基因表达水平的趋势。这项研究表明，结合11β-HSD1抑制和PPAR-γ激动剂可以额外减少肝脏脂肪变性和甘油三酯血症，这最终可能被证明是有用的治疗。《国际肥胖杂志》(2009年)33601604；DOI：10.1038/ijo.2009.33；在线出版
Both 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD1) inhibition and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonism reduce liver and plasma lipids in rodents through partly distinct mechanisms. This study aimed to assess their additivity of action on liver and plasma lipids in a model of diet-induced steatosis. Rats were fed an obesogenic diet and were treated either with an 11 beta-HSD1 inhibitor (Compound A, 3mg kg(-1) day(-1)) or rosiglitazone (RSG, 5mg kg(-1) day(-1)) or both for 6 weeks. Compound A and RSG reduced liver steatosis and triglyceridemia, and did so additively when given in combination. The 11 beta-HSD1 inhibitor had no effect on serum adiponectin, but increased liver adiponectin receptor type 2 (Adipo-R2) mRNA levels. Conversely, RSG increased serum adiponectin, a likely mediator of its antisteatotic action, but had no effect per se on the Adipo-R2 expression. mRNA levels of representative genes of fatty acid oxidation tended to be increased by both compounds. The study shows that combined 11 beta-HSD1 inhibition and PPAR-gamma agonism additively reduce liver steatosis and triglyceridemia, which may eventually prove therapeutically useful. International Journal of Obesity (2009) 33, 601-604; doi:10.1038/ijo.2009.33; published online 17 February 2009