Brain-derived Neurotrophic Factor Regulates Energy Expenditure Through the Central Nervous System in Obese Diabetic Mice

It has been previously demonstrated that brain-derivedneurotrophic factor (BDNF) regulates glucosemetabolism and energy expenditure in rodentdiabetic models such as C57BL/KsJ-lepr^db/lepr^db (db/db) mice. Central administration of BDNF hasbeen found to reduce blood glucose in db/db mice,suggesting that BDNF acts through the central nervoussystem. In the present study we have expandedthese investigations to explore the effect of centraladministration of BDNF on energy metabolism. Intracerebroventricularadministration of BDNF lowered blood glucose and increased pancreatic insulincontent of db/db mice compared with vehicle-treatedpellet pair-fed db/db mice. While body temperaturesof the pellet pair-fed db/db mice given vehicle werereduced because of restricted food supply in thispair-feeding condition, BDNF treatment remarkablyalleviated the reduction of body temperature suggestingthe enhancement of thermogenesis. BDNFenhanced norepinephrine turnover and increaseduncoupling protein-1 mRNA expression in the interscapularbrown adipose tissue. Our evidence indicatesthat BDNF activates the sympathetic nervoussystem via the central nervous system and regulatesenergy expenditure in obese diabetic animals.