It has been previously demonstrated that brain-derived
neurotrophic factor (BDNF) regulates glucose
metabolism and energy expenditure in rodent
diabetic models such as C57BL/KsJ-leprdb/leprdb (db/db) mice. Central administration of BDNF has
been found to reduce blood glucose in db/db mice,
suggesting that BDNF acts through the central nervous
system. In the present study we have expanded
these investigations to explore the effect of central
administration of BDNF on energy metabolism. Intracerebroventricular
administration of BDNF lowered blood glucose and increased pancreatic insulin
content of db/db mice compared with vehicle-treated
pellet pair-fed db/db mice. While body temperatures
of the pellet pair-fed db/db mice given vehicle were
reduced because of restricted food supply in this
pair-feeding condition, BDNF treatment remarkably
alleviated the reduction of body temperature suggesting
the enhancement of thermogenesis. BDNF
enhanced norepinephrine turnover and increased
uncoupling protein-1 mRNA expression in the interscapular
brown adipose tissue. Our evidence indicates
that BDNF activates the sympathetic nervous
system via the central nervous system and regulates
energy expenditure in obese diabetic animals.