Multiple roles of PPARalpha in brown adipose tissue under constitutive and cold conditions

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the nuclear receptor family, regulating fatty acid degradation in many organs. Two-dimensional SDS-PAGE of brown adipose tissue (BAT) from PPARalpha-null mice produced a higher-density spot. Proteomic analysis indicated that the protein was pyruvate dehydrogenase beta (PDHbeta). To observe PDHbeta regulation in BAT, the organ was stimulated by long-term cold exposure, and the activities of associated enzymes were investigated. Histological and biochemical analyses of BAT showed a significant decrease in the triglyceride content in wild-type mice and some degree of decrease in PPARalpha-null mice on cold exposure. Analyses of molecules related to glucose metabolism showed that the expression of PDHbeta is under PPARalpha-specific regulation, and that glucose degradation ability may decrease on cold exposure. In contrast, analyses of molecules related to fatty acid metabolism showed that numerous PPARalpha/gamma target molecules are induced on cold exposure, and that fatty acid degradation ability in wild-type mice is markedly enhanced and also increases to same degree in PPARalpha-null mice on cold exposure. Thus, this study proposes novel and multiple roles of PPARalpha in BAT.