Nedergaard Jan, Petrovic Natasa, Lindgren Eva M, Jacobsson Anders, Cannon Barbara
The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden.
Biochim Biophys Acta. 2005 May 30;1740(2):293-304. doi: 10.1016/j.bbadis.2005.02.003. Epub 2005 Feb 22.
The effects of fatty acids and retinoic acid (carotene) on brown adipose tissue differentiation are mediated by activation of the transcription factors PPARgamma and PPARalpha in combination with RXR. There is good support for the idea that activated PPARgamma promotes adipogenesis also in brown adipose tissue. However, the issue is more complex concerning the full differentiation to the brown adipocyte phenotype, particularly the expression of the brown-fat-specific marker UCP1. The effect of norepinephrine on PPARgamma gene expression, at least in-vitro, is negative, PPARgamma-ablated brown adipose tissue can express UCP1, and PGC-1alpha coactivates other transcription factors (including PPARalpha); thus, the significance of PPARgamma for the physiological control of UCP1 gene expression is not settled. However, importantly, the effects of PPAR agonists demonstrate the existence of a pathway for brown adipose tissue recruitment that is not dependent on chronic adrenergic stimulation and may be active in recruitment conditions such as prenatal and prehibernation recruitment. The ability of chronic PPARgamma agonist treatment to promote the occurrence of brown-fat features in white adipose tissue-like depots implies a role in anti-obesity treatment, but this will only be effective if the extra thermogenic capacity is activated by adrenergic stimulation.
脂肪酸和视黄酸（胡萝卜素）对棕色脂肪组织分化的影响是通过转录因子PPARγ和PPARα与RXR结合激活来介导的。有充分证据支持激活的PPARγ在棕色脂肪组织中也促进脂肪生成这一观点。然而，关于完全分化为棕色脂肪细胞表型，特别是棕色脂肪特异性标志物UCP1的表达，问题更为复杂。去甲肾上腺素对PPARγ基因表达的影响，至少在体外是负面的，PPARγ基因敲除的棕色脂肪组织可以表达UCP1，并且PGC-1α可共激活其他转录因子（包括PPARα）；因此，PPARγ对UCP1基因表达的生理控制的重要性尚未确定。然而，重要的是，PPAR激动剂的作用表明存在一条棕色脂肪组织募集途径，该途径不依赖于慢性肾上腺素能刺激，并且可能在诸如产前和冬眠前募集等募集条件下起作用。慢性PPARγ激动剂治疗促进白色脂肪组织样脂肪库中棕色脂肪特征出现的能力意味着其在抗肥胖治疗中的作用，但只有在肾上腺素能刺激激活额外的产热能力时才会有效。
