PMID- 21856381 OWN - NLM STAT- MEDLINE DCOM- 20120625 LR - 20240320 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 194 DP - 2011 Oct 27 TI - Reduction of high-fat diet-induced obesity after chronic administration of brain-derived neurotrophic factor in the hypothalamic ventromedial nucleus. PG - 36-52 LID - 10.1016/j.neuroscience.2011.07.079 [doi] AB - An acute injection of brain-derived neurotrophic factor (BDNF) in the hypothalamic ventromedial nucleus (VMN) decreases body weight by reducing feeding and increasing energy expenditure (EE) in animals on standard laboratory chow. Animals have divergent responses to high-fat diet (HFD) exposure, with some developing obesity and others remaining lean. In the current study, we tested the hypothesis that BDNF in the VMN reduces HFD-induced obesity. Seventy-two 10-week old rats were allowed HFD ad libitum for 8 weeks and then prepared with bilateral VMN cannulae. Animals were then divided into tertiles based on their fat mass rank: high, intermediate, and low (H, I, and L). Each group was further divided into two subgroups: BDNF (1 mug) or control (artificial cerebrospinal fluid, aCSF); they were then injected every other day for 20 days according to subgroup. Energy intake, body weight, and body composition were measured. Other metabolic indexes were measured before and after treatment. In parallel, another 12 rats were fed control diet (CD), VMN-cannulated, and injected with aCSF. HFD exposure induced obesity in the H group, with a significant increase in energy intake, body weight, fat mass, liver size, and serum glucose, insulin, and leptin. BDNF significantly reduced body weight and fat mass in all phenotypes, while it reduced energy intake only in the I group. However, BDNF increased EE, spontaneous physical activity, and fat oxidation in the H group, suggesting that BDNF-induced EE elevation contributed to reduction of body weight and fat mass. Chronic VMN BDNF reduced insulin elevation and/or reversed hyperleptinemia. These data suggest that the VMN is an important site of action for BDNF reduction of HFD-induced obesity. CI - Published by Elsevier Ltd. FAU - Godar, R AU - Godar R AD - Veterans Affairs Medical Center, One Veterans Drive, Research Route 151, Minneapolis, MN 55417, USA. FAU - Dai, Y AU - Dai Y FAU - Bainter, H AU - Bainter H FAU - Billington, C AU - Billington C FAU - Kotz, C M AU - Kotz CM FAU - Wang, C F AU - Wang CF LA - eng GR - R01 DK080782/DK/NIDDK NIH HHS/United States GR - R01 DK080782-03/DK/NIDDK NIH HHS/United States GR - 1R01DK080782/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20110805 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Leptin) SB - IM MH - Adipose Tissue/physiology MH - Animals MH - Brain-Derived Neurotrophic Factor/*physiology/therapeutic use MH - Contraindications MH - Diet, High-Fat/*adverse effects MH - Disease Models, Animal MH - Energy Intake/physiology MH - Hyperinsulinism/prevention & control MH - Leptin/antagonists & inhibitors/blood MH - Male MH - Obesity/*metabolism/physiopathology/*therapy MH - Rats MH - Rats, Sprague-Dawley MH - Ventromedial Hypothalamic Nucleus/*metabolism/physiology PMC - PMC3190117 MID - NIHMS317270 EDAT- 2011/08/23 06:00 MHDA- 2012/06/26 06:00 PMCR- 2012/10/27 CRDT- 2011/08/23 06:00 PHST- 2011/01/28 00:00 [received] PHST- 2011/06/24 00:00 [revised] PHST- 2011/07/13 00:00 [accepted] PHST- 2011/08/23 06:00 [entrez] PHST- 2011/08/23 06:00 [pubmed] PHST- 2012/06/26 06:00 [medline] PHST- 2012/10/27 00:00 [pmc-release] AID - S0306-4522(11)00925-0 [pii] AID - 10.1016/j.neuroscience.2011.07.079 [doi] PST - ppublish SO - Neuroscience. 2011 Oct 27;194:36-52. doi: 10.1016/j.neuroscience.2011.07.079. Epub 2011 Aug 5.