PPARγ in the control of brown adipocyte differentiation

The effects of fatty acids and retinoic acid (carotene) on brown adipose tissue differentiation are mediated by activation of the transcription factors PPARγ and PPARα in combination with RXR. There is good support for the idea that activated PPARγ 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 PPARγ gene expression, at least in-vitro, is negative, PPARγ-ablated brown adipose tissue can express UCP1, and PGC-1α coactivates other transcription factors (including PPARα); thus, the significance of PPARγ 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 PPARγ 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.