Enhanced sympathetic activity in mice with brown adipose tissue transplantation (transBATation)

Abstract

Brown adipose tissue (BAT) burns calories to produce heat, and is thus relevant to energy balance. Interscapular BAT (IBAT) of donor mice was transplanted into recipient mice (transBATation). To test whether transBATation counteracts high-fat diet (HFD)-induced obesity, some sham-operated and recipient mice were fed a HFD (HFD-sham, HFD-trans) while others remained on a standard chow (chow-sham, chow-trans). HFD-trans mice had lower body weight and fat and greater energy expenditure, but similar caloric intake compared with HFD-sham mice. We hypothesized that HFD-trans mice had elevated sympathetic activity compared with HFD-sham mice, contributing to increased energy expenditure and fuel mobilization. This was supported by findings that HFD-trans mice had greater energy expenditure during a norepinephrine challenge test and higher core temperatures after cold exposure than did HFD-sham mice, implicating enhanced whole-body metabolic response and elevated sympathetic activity. Additionally, transBATation selectively increased sympathetic drive to some, but not all, white adipose tissue depots and skeletal muscles, as well as the endogenous IBAT, heart, and liver. Collectively, transBATation confers resistance to HFD-induced obesity via increase in whole-body sympathetic activity, and differential activation of sympathetic drive to some of the tissues involved in energy expenditure and fuel mobilization.

Keywords: BAT; Cold exposure; EDL; EE; EWAT; Energy expenditure; HFD; IBAT; IWAT; LGAS; MGAS; MWAT; NETO; Norepinephrine challenge; Norepinephrine turnover; PBS; PGC1α; RWAT; SNS; TH; Tyrosine hydroxylase; UCP1; Visceral white adipose tissue; WAT; brown adipose tissue; energy expenditure; epididymal white adipose tissue; extensor digitorum longus; high-fat diet; inguinal white adipose tissue; interscapular brown adipose tissue; lateral gastrocnemius; medial gastrocnemius; mesenteric white adipose tissue; norepinephrine turnover; peroxisome proliferator-activated receptor gamma coactivator-1α; phosphate-buffered saline; retroperitoneal white adipose tissue; sympathetic nervous system; tyrosine hydroxylase; uncoupling protein 1; white adipose tissue.