A milk interleukin-10/gut secretin axis promotes brown adipose tissue thermogenesis in breastfeeding newborns

Mammalian newborns must activate thermogenesis to adapt to colder extrauterine temperatures. Brown adipose tissue plays a key role in this context through uncoupling protein-1-dependent mitochondrial respiration. The current model proposes that cortisol, catecholamine, and thyroid hormone surges after delivery drive neonatal thermal adaptation; however, this model lacks a mother-newborn interface factor promoting cold tolerance during early life. Here, we show that interleukin-10 is present in milk and stimulates neonatal thermogenesis. Interleukin-10 receptor B is co-expressed with secretin in gut epithelial cells, and milk and exogenous interleukin-10 stimulate gut secretin expression, increasing thermogenesis and cold adaptation. In humans and mice, the neonate's body temperature determines the amount of interleukin-10 in milk. Interleukin-10 acts through CREB to increase secretin release from the newborn intestine, while secretin blockade inhibits interleukin-10-induced cold adaptation. Thus, we identify a milk interleukin-10/gut secretin axis that stimulates newborn brown adipose tissue non-shivering thermogenesis.