C5aR1-positive adipocytes mediate non-shivering thermogenesis in neonatal mice

Abstract

Brown adipose tissue (BAT) plays an important role in maintaining body temperature in newborn mammals; however, its mechanisms remain poorly understood. Here, we report the identification of a special population of brown adipose tissue-derived stromal cells (ASCs) in neonatal mice that highly express CD45 and can be differentiated into adipocytes with lower thermogenic ability. These CD45⁺ adipocytes also characteristically contained complement C5a receptor 1(C5aR1) on the cell membrane. C5ar1 deficiency in BAT resulted in an apparent immaturity of adipocytes and cold intolerance in neonatal mice. Mechanistically, loss of C5aR1 in these CD45⁺ brown adipocytes caused an increase in the secretion of plate factor four (PF4) from these cells, suppressing the maturity of neighboring brown adipocytes. Overall, our results indicated that the accumulation of C5aR1 positive brown adipocyte in neonatal BAT is essential for thermoregulation in newborn mice, which unveiled the regulatory mechanism of BAT-mediated thermogenesis in newborns.