Acute effects of brain-derived neurotrophic factor on energy expenditure in obese diabetic mice.
OBJECTIVE
We recently demonstrated that chronic treatment with brain-derived neurotrophic factor (BDNF) regulates energy expenditure in obese diabetic C57BL/KsJ-db/db mice. In this study, we investigated the acute effects of BDNF on energy expenditure.


METHODS
After BDNF was singly administered to male db/db mice (aged 10-12 weeks), their body temperature and whole body glucose oxidation were measured. Their norepinephrine (NE) turnover and uncoupling protein (UCP) 1 expression in interscapular brown adipose tissue (BAT) were also analyzed.


RESULTS
Even though the body temperatures of hyperphagic db/db mice dropped remarkably in a 24 h period after food deprivation, only a single subcutaneous administration of BDNF significantly prevented the reduction of body temperature. BDNF was also observed to have similar efficacy in cold exposure experiments at 15 degrees C. Respiratory excretion of (14)CO(2) after intravenous injection of D-[(14)C(U)]-glucose was significantly increased by BDNF administration, indicating that BDNF increases whole-body glucose oxidation. BDNF administered intracerebroventricularly was also able to prevent the reduction of body temperature of db/db mice. To clarify the BDNF action mechanism we examined NE turnover in BAT. Four hours after a single administration, BDNF reduced NE content in the presence of the tyrosine hydroxylase inhibitor, alpha-methyl-P-tyrosine methyl ester, indicating enhanced NE turnover in BAT. BDNF also increased the expression of the UCP1 mRNA and protein in BAT.


CONCLUSIONS
These data indicate that BDNF rapidly regulates energy metabolism in obese diabetic animals, partly through activating the sympathetic nervous system and inducing UCP1 gene expression in BAT.
Tsuchida
A
A
Sumitomo Pharmaceuticals Co. Ltd, Discovery Research Laboratories II, Osaka, Japan.
Nonomura
T
T
Ono-Kishino
M
M
Nakagawa
T
T
Taiji
M
M
Noguchi
H
H
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D001831:Body Temperature / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D003920:Diabetes Mellitus / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D007473:Ion Channels; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D024101:Mitochondrial Proteins; D009638:Norepinephrine / Q000378:metabolism*; D009765:Obesity; D012333:RNA, Messenger / Q000032:analysis; D022722:Thermogenesis / Q000187:drug effects; D000071256:Uncoupling Protein 1
D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D009638:Norepinephrine