Differential Sympathetic Activation of Adipose Tissues by Brain-Derived Neurotrophic Factor

Abstract

Centrally administered brain-derived neurotrophic factor (BDNF) decreases body adiposity beyond what can be accounted for by decreased food intake, implying enhanced lipid metabolism by BDNF. Consistent with this notion, intracerebroventricular (icv) injection of BDNF in rats increased the expression of lipolytic enzymes in white adipose tissues (WAT) and increased circulating concentrations of lipolytic products without changing the levels of adrenal gland hormones. This suggests that central BDNF-induced lipid mobilization is likely due to sympathetic neural activation, rather than activation of the adrenocortical or adrenomedullary system. We hypothesized that BDNF activated sympathetic innervation of adipose tissues to regulate lipolysis. Rats with unilateral denervation of interscapular brown adipose tissue (BAT) and different WAT depots received icv injections of saline or BDNF. Both intact and denervated adipose tissues were exposed to the same circulating factors, but denervated adipose tissues did not receive neural signals. Norepinephrine (NE) turnover (NETO) of BAT and WAT was assessed as a measure of sympathetic activity. Findings revealed that central BDNF treatment induced a change in NETO in some but not all the adipose tissues tested. Specifically, greater NETO rates were found in BAT and gonadal epididymal WAT (EWAT), but not in inguinal WAT (IWAT) or retroperitoneal WAT (RWAT), of BDNF-treated rats compared to saline-treated rats. Furthermore, intact innervation was necessary for BDNF-induced NETO in BAT and EWAT. In addition, BDNF increased the expression of lipolytic enzymes in both intact and denervated EWAT and IWAT, suggesting that BDNF-induced WAT lipolysis was independent of intact innervation. To summarize, centrally administered BDNF selectively provoked sympathetic drives to BAT and EWAT that was dependent on intact innervation, while BDNF also increased lipolysis in a manner independent of intact innervation.