BMPR2 Deficiency Inhibits Fatty Acid Oxidation and Renders White Adipocytes Vulnerable to TNFα-Induced Apoptosis

Adipocyte apoptosis is a normal process for adipose tissue self-renewal, however overt apoptosis is pathologically involved in both obesity and lipodystrophy. Pro-inflammatory cytokines are generally regarded as inducers for adipocyte apoptosis, but whether some innate defects of adipocytes affect their apoptotic susceptibility has rarely been studied. Here, we found BMPR2 knockout adipocytes were prone to TNFα-induced apoptosis both in vivo and ex vivo. BMPR2 deficiency in adipocytes inhibited phosphorylation of lipid-droplet-coating protein, perilipin, and impaired lipolysis stimulated by TNFα. Impaired lipolysis failed to supply fatty acid for mitochondrial oxidation, oxidative phosphorylation and stimulated mitochondria-mediated apoptosis. These results suggest that the innate functional integrity of adipocytes determines their ability to survive when interacting with inflammatory factors, which may explain why adipocytes among individuals show discrepancy for apoptotic responses to the same inflammatory pressure. Funding: This study was supported by the National Natural Science Foundation of China (grant no. 31670787 to S.W.Q. and 31571471 to Q.Q.T.), the Ministry of Science and technology of China grant (2013CB530601 to Q.Q.T), and the State Key Program of National Natural Science Foundation of China (grant no. 81390353 to Q.Q.T.). The research was partially supported by 985 Project (985-YFX0302). Declaration of Interest: All authors have no competing interests to declare, financial or otherwise. Ethical Approval: This study was approved by the ethics committees of Shanghai Medical College, Fudan University and was in accordance with the principle of the Helsinki Declaration II. The written informed consent was obtained from each participant.