The Role Of PNPLA7 In Mouse Adipose Tissue Adaptive Thermogenesis

Adipose tissue is one of the most important metabolic organs in mammals.There are three types of adipose tissues:white adipose tissue(WAT),brown adipose tissue(BAT)and beige adipose tissue.The dominant function of white adipose tissue is to store the excess energy in the form of TAG and as energy supplier for peripheral tissue under certain circumstance of such as starvation condition.Brown adipose tissue is rich in mitochondrial and its main function is thermogenesis.Beige adipose tissue could be induced from white adipose tissue under specific conditions such as cold exposure or drug treatment.Its functions are similar to those of brown adipose tissue,and both of them are commonly known as thermogenic adipose tissue.The activation of thermogenic adipose tissue can be used to prevent obesity and increase insulin sensitivity.In this study,we found that PNPLA7 protein was enriched in interscapular BAT followed by subcutaneous inguinal WAT(iWAT)and visceral epididymal WAT(eWAT).The protein level of PNPLA7 in BAT as well as in iWAT was significantly decreased in mice after cold exposure and β3-adrenergic agonist CL316243 treatment.On the contrary,the UCP1 protein level was significantly induced in fat depots of these mice.In addition,the expression levels of PNPLA7 were increased but UCP1 were decreased in BAT of ob/ob mice.These results indicated that PNPLA7 may involve in the process of adaptive thermogenesis in BAT,and its regulation was negatively correlated with that of UCP1.To further investigate the physiological role of PNPLA7 in adipose tissue,adipose tissue specific transgenic mouse aP2-PNPLA7Tg was generated.Although,overexpression of PNPLA7 in adipose tissue has no effect on body fat composition,insulin sensitivity and whole body energy expenditure,overexpression of PNPLA7 casuses WAT-like transition of BAT after high fat diet feeding.The phenomenon associated with decreased expression level of genes involved in theromogenesis,fatty acid oxidation,mitochondrial oxidative phosphorylation(OXPHOS)such as Ucpl,Ppara,Cpt-1β,Sdhb et al.Meanwhile,the protein levels of UCP1 and PGC1 a were significantly lower in BAT of aP2-PNPLA7Tg mice compared with wild type mice.The transition of BAT to WAT-like fat of aP2-PNPLA7Tg mice leads to less able to defend their body temperature in the fact to acute cold stress.Consistently,overexpression of PNPLA7 in adipose tissue abolished the stimulatory effect of prolonged cold exposure on the adaptive thermogensis of BAT.Further results indicated that PNPLA7 transgene manipulates the process of browning and mitochondria function of iWAT.Taken together,our study demonstrated that PNPLA7 is a novel important regulator of adaptive thermogenesis in BAT and browning in iWAT of mice.Although,the precise molecular mechanism basis of PNPLA7 underlying the regulation of function of adipose tissue remains to be resolved,these finding provide a new therapeutic target for the treatment of adipose tissue metabolic diseases.