Brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus increases energy expenditure by elevating metabolic rate.
Brain-derived neurotrophic factor (BDNF) decreases food intake and body weight, but few central sites of action have been identified. The hypothalamic paraventricular nucleus (PVN) is important in energy metabolism regulation, and expresses both BDNF and its receptor. We tested three hypotheses: 1) PVN BDNF reduces feeding and increases energy expenditure (EE), 2) PVN BDNF-enhanced thermogenesis results from increased spontaneous physical activity (SPA) and resting metabolic rate (RMR), and 3) PVN BDNF thermogenic effects are mediated, in part, by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). BDNF (0.5 microg) was injected into the PVN of Sprague-Dawley rats; and oxygen consumption, carbon dioxide production, food intake, and SPA were measured for 24 h in an indirect calorimeter. SPA was also measured in open-field activity chambers for 48 h after BDNF injection. Animals were killed 6 or 24 h after BDNF injection, and BAT UCP1 gene expression was measured with quantitative real-time PCR. BDNF significantly decreased food intake and body weight gain 24 h after injection. Heat production and RMR were significantly elevated for 7 h immediately after BDNF injection. BDNF had no effect on SPA, but increased UCP1 gene expression in BAT at 6 h, but not 24 h after injection. In conclusion, PVN BDNF reduces body weight by decreasing food intake and increasing EE consequent to increased RMR, which may be due, in part, to BAT UCP1 activity. These data suggest that the PVN is an important site of BDNF action to influence energy balance.
Wang
ChuanFeng
C
Veterans Affairs Medical Center, Research Service (151), One Veterans Drive, Minneapolis, MN 55417, USA. cwang@umn.edu
Bomberg
Eric
E
Billington
Charles
C
Levine
Allen
A
Kotz
Catherine M
CM
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D002153:Calorimetry, Indirect; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008660:Metabolism / Q000187:drug effects*; D008845:Microinjections; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071256:Uncoupling Protein 1; D015430:Weight Gain / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1