Sympathetic nerve innervation is required for beigeing in white fat

It is increasingly recognized that activation of beige adipocyte thermogenesis by pharmacological or genetic approaches increases energy expenditure and alleviates obesity. Sympathetic nervous system (SNS) directly innervating brown adipose tissue (BAT) and white adipose tissue (WAT) plays a key role in promoting nonshivering thermogenesis. However, direct evidence that supports the importance of SNS innervation for beige adipocyte formation is still lacking, and the significance of beige adipocyte thermogenesis in protection of body temperature during cold challenge is not clear. Here we tested the necessity of SNS innervation into WAT for beige adipocyte formation in mice with defective brown fat thermogenesis via interscapular BAT (iBAT) SNS denervation. SNS denervation was achieved by microinjection of 6-hydroxydopamine (6-OHDA), a selective neurotoxin to SNS nerves, into iBAT, inguinal WAT (iWAT), or both. The partial chemical denervation of iBAT SNS down-regulated UCP-1 protein expression in iBAT demonstrated by immunoblotting and immunohistochemical measurements. This was associated with an up-regulation of UCP1 protein expression and enhanced formation of beige cells in iWAT of mice with iBAT SNS denervation. In contrast, the chemical denervation of iWAT SNS completely abolished the upregulated UCP-1 protein and beige cell formation in iWAT of mice with iBAT SNS denervation. Our data demonstrate that SNS innervation in WAT is required for beige cell formation during cold-induced thermogenesis. We conclude that there exists a coordinated thermoregulation for BAT and WAT thermogenesis via a functional cross talk between BAT and WAT SNS.