A role for central nervous system PPAR-γ in the regulation of energy balance.
A role for central nervous system PPAR-γ in the regulation of energy balance.
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作者：
过氧化物酶体增殖物激活受体(PPAR)-γ是一种核受体，可被脂质激活，诱导参与脂质和葡萄糖代谢的基因表达，从而将营养信号转化为代谢结果。PPARγ是噻唑烷二酮（TZD）类胰岛素增敏药物的靶点，这些药物已被广泛用于治疗2型糖尿病（T2DM）。服用tzd治疗的一个常见副作用是体重增加。在这里，我们报道了中枢神经系统（CNS） PPARγ在调节能量平衡中的新作用。我们发现，通过TZDs或下丘脑过度表达VP16-PPARγ融合蛋白，中枢神经系统的急性和慢性激活都能导致大鼠的正能量平衡。用药物拮抗剂或shRNA阻断CNS PPARγ的内源性激活，导致负能量平衡，恢复高脂饮食（HFD）喂养大鼠的瘦素敏感性，并阻断口服TZD治疗的贪食反应。这些发现对TZD药物的广泛临床应用和了解饮食性肥胖的病因具有重要意义。
The peroxisome proliferator activated receptor (PPAR)-γ is a nuclear receptor that is activated by lipids to induce the expression of genes involved in lipid and glucose metabolism, thereby converting nutritional signals into metabolic consequences. PPARγ is the target of the thiazolidinedione (TZD)-class of insulin-sensitizing drugs, which have been widely prescribed to treat Type 2 Diabetes Mellitus (T2DM). A common side effect of treatment with TZDs is weight gain. Here we report a novel role for central nervous system (CNS) PPARγ in the regulation of energy balance. We found that both acute and chronic activation of CNS PPARγ, by TZDs or by hypothalamic over-expression of a VP16-PPARγ fusion protein, led to positive energy balance in rats. Blocking the endogenous activation of CNS PPARγ, with pharmacological antagonists or with shRNA, led to negative energy balance, restored leptin-sensitivity in high-fat diet (HFD)-fed rats, and blocked the hyperphagic response to oral TZD treatment. These findings have implications for the widespread clinical use of TZD drugs and for understanding the etiology of diet-induced obesity.
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DOI：
10.1073/pnas.0501744102
发表时间：
2005-06-28
影响因子：
11.1
作者：
Zhang, H;Zhang, AH;Yang, TX
通讯作者：
Yang, TX
影响因子：
3.3
作者：
Moreno, S;Farioli-Vecchioli, S;Cerù, MP
通讯作者：
Cerù, MP
影响因子：
--
作者：
Li, Y;Lazar, MA
通讯作者：
Lazar, MA
影响因子：
16
作者：
Rosen, ED;Sarraf, P;Mortensen, RM
通讯作者：
Mortensen, RM
影响因子：
3.3
作者：
Scarpace, PJ;Matheny, M;Tümer, N
通讯作者：
Tümer, N