Peroxisome proliferator-activated receptor-γ-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status
Peroxisome proliferator-activated receptor-γ-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status
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DOI：
10.1210/en.2007-1553
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发表时间：
2008-05-01
期刊：
影响因子：
4.8
通讯作者：
Deshaies, Yves
中科院分区：
文献类型：
--
作者：
Festuccia, William T.;Oztezcan, Serdar;Deshaies, Yves
过氧化物酶体增殖物激活受体-γ（PPAR γ）激活上调啮齿动物白色和棕色脂肪组织（WAT和BAT）中的产热相关基因，而不增加全身能量消耗。我们在这里测试了这种解离是否是通过PPAR γ激活对WAT和BAT以及甲状腺轴组件的交感神经活动的负调制的结果。给予雄性Sprague道利大鼠7天的PPAR γ激动剂罗格列酮（15 mg/kg中心点d）增加了摄食量（10%）、饲料效率（31%）、体重增加（45%）、自发运动活动（60%）、BAT和WAT质量，并降低了全身耗氧量。与合成代谢环境一致，罗格列酮显著降低对BAT和WAT的交感神经活性（> 50%）和甲状腺状态，如血浆甲状腺激素（T-4和T-3）水平以及BAT和肝脏T-3生成酶2型碘甲状腺原氨酸脱碘酶（-40%）和1型脱碘酶（-32%）的mRNA水平降低所证明。罗格列酮还降低BAT中甲状腺激素受体（THR）亚型α 1（-34%）和β（-66%）以及腹膜后WAT中亚型α 1（-20%）和α 2（-47%）的mRNA水平。这些代谢效应与特定下丘脑核团中促能量消耗肽CRH和CART的mRNA水平降低有关。然而，罗格列酮的直接中枢作用不太可能，因为其脑摄取量低，且脑室内给药缺乏代谢作用。总之，BAT交感神经活性和甲状腺状态的减少似乎至少部分地解释了PPAR γ诱导的能量消耗减少以及产热基因表达上调不会转化为体内全身产热的功能刺激的事实。
Peroxisome proliferator-activated receptor-gamma (PPAR gamma) activation up-regulates thermogenesis-related genes in rodent white and brown adipose tissues (WAT and BAT) without increasing whole-body energy expenditure. We tested here whether such dissociation is the result of a negative modulation of sympathetic activity to WAT and BAT and thyroid axis components by PPAR gamma activation. Administration of the PPAR gamma agonist rosiglitazone (15 mg/kg center dot d) for 7 d to male Sprague Dawley rats increased food intake (10%), feed efficiency (31%), weight gain (45%), spontaneous motor activity (60%), and BAT and WAT mass and reduced whole-body oxygen consumption. Consistent with an anabolic setting, rosiglitazone markedly reduced sympathetic activity to BAT and WAT(> 50%) and thyroid status as evidenced by reduced levels of plasma thyroid hormones (T-4 and T-3) and mRNA levels of BAT and liver T-3-generating enzymes iodothyronine type 2 (-40%) and type 1 (-32%) deiodinases, respectively. Rosiglitazone also decreased mRNA levels of the thyroid hormone receptor (THR) isoforms alpha 1 (-34%) and beta (-66%) in BAT and isoforms alpha 1 (-20%) and alpha 2 (-47%) in retroperitoneal WAT. These metabolic effects were associated with a reduction in mRNAlevels of the pro-energy expenditure peptides CRH and CART in specific hypothalamic nuclei. A direct central action of rosiglitazone is, however, unlikely based on its low brain uptake and lack of metabolic effects of intracerebroventricular administration. In conclusion, a reduction in BAT sympathetic activity and thyroid status appears to, at least partly, explain the PPAR gamma-induced reduction in energy expenditure and the fact that up-regulation of thermogenic gene expression does not translate into functional stimulation of whole-body thermogenesis in vivo.