Cold-inducible PPA1 is critical for the adipocyte browning in mice

• Published in: Biochemical and biophysical research communications Vol. 677; pp. 45 - 53
• Main Authors: Sun, Yue, Yao, Jingxin, Lu, Chang, Yang, Nan, Han, Xiao, Lin, Haiyan, Yin, Ye
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.2023
• Subjects: Adipocytes, Brown - metabolism; Adipose Tissue, Brown - metabolism; Adipose Tissue, White - metabolism; Animals; brown/beige adipocyte; Inorganic Pyrophosphatase - genetics; Inorganic Pyrophosphatase - metabolism; Mice; Mice, Inbred C57BL; Mitochondrial dysfunction; NRF1; Obesity; Obesity - genetics; Obesity - metabolism; PPA1; Thermogenesis - genetics; brown/beige adipocyte; Obesity; Mitochondrial dysfunction; NRF1; PPA1
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2023.08.009

Promoting the thermogenic capacity of brown/beige adipocytes is becoming a promising strategy to counteract obesity and related metabolic diseases. Inorganic pyrophosphatase 1 (PPA1) is an enzyme that catalyzes the hydrolysis of PPi to Pi, and its presence is required for anabolism to take place in cells. Our previous study demonstrated the importance of PPA1 in maintaining adipose tissue function and whole-body metabolic homeostasis. In this study, we found that the expression of PPA1 was positively associated with the thermogenic capacity of brown/beige adipocytes. PPA1+/− mice exhibited less browning capacity in subcutaneous white adipose tissue compared to wild-type mice and also showed apparent cold intolerance. We found that decreased PPA1 abundance may lead to mitochondrial dysfunction and inhibited adipocyte browning both in vivo and in vitro. Furthermore, our study also revealed that PPA1 worked as a new target gene of nuclear respiratory factor 1 (NRF1), a major transcription regulator of mitochondrial biogenesis. Together, our findings indicated an essential role of PPA1 in mitochondrial function and browning in adipocytes and suggested PPA1 as a new therapeutic target for increasing thermogenesis to combat obesity and metabolic diseases. •Expression of PPA1 positively associated with the abundance of browning markers.•Reduced PPA1 expression in adipose tissue inhibited the browning process and thermogenic capacity in vivo.•Loss of PPA1 inhibited brown adipogenesis by impairing mitochondrial function.•PPA1 maintains mitochondrial function as a new target gene of NRF1 (nuclear respiratory factor 1).