PMID- 12704399
OWN - NLM
STAT- MEDLINE
DCOM- 20030519
LR  - 20140603
VI  - 27
IP  - 5
DP  - 2003 May
TI  - Anti-obesity and anti-diabetic effects of brain-derived neurotrophic factor in 
      rodent models of leptin resistance.
PG  - 557-65
AB  - OBJECTIVE: Obesity in rodents and humans is mostly associated with elevated 
      plasma leptin concentrations, suggesting a new pathological concept of 'leptin 
      resistance'. We have demonstrated that brain-derived neurotrophic factor (BDNF) 
      can improve obesity and diabetes of C57BL/KsJ db/db (db/db) mice. In this study, 
      we investigated whether or not BDNF is effective in two different models of 
      leptin resistance, an acquired model and a genetic model. DESIGN: C57BL/6J mice 
      rendered obese by consumption of a high-fat diet (diet-induced obesity (DIO) 
      mice) were used as an acquired model and lethal yellow agouti mice (KKA(y) mice) 
      as a genetic model of leptin resistance. Food intake and glucose metabolism were 
      studied after acute or repetitive administration of BDNF. RESULTS: 
      Intraperitoneal administration of BDNF (10 mg/kg, twice/day) significantly 
      reduced cumulative food intake of DIO and KKA(y) mice, whereas they were 
      unresponsive to leptin administration. Repetitive subcutaneous administration of 
      BDNF (10 mg/kg daily for 6 days) reduced food intake and improved impaired 
      glucose tolerance in DIO mice. Pair feeding of vehicle-treated DIO mice with the 
      same amount of chow consumed by the BDNF-treated group did not improve the 
      impaired glucose homeostasis, indicating that the antidiabetic effect is not due 
      to decreased food intake. We also observed that BDNF is effective in improving 
      obesity and diabetes of KKA(y) mice. CONCLUSION: This study demonstrated 
      antiobesity and antidiabetic effects of BDNF in two different models of leptin 
      resistance, thereby suggesting the therapeutic potential of BDNF in the treatment 
      of leptin-resistant obesity and diabetes.
FAU - Nakagawa, T
AU  - Nakagawa T
AD  - Discovery Research Laboatories I, Sumitomo Pharmaceuticals Research Division, 
      Osaka, Japan.
FAU - Ogawa, Y
AU  - Ogawa Y
FAU - Ebihara, K
AU  - Ebihara K
FAU - Yamanaka, M
AU  - Yamanaka M
FAU - Tsuchida, A
AU  - Tsuchida A
FAU - Taiji, M
AU  - Taiji M
FAU - Noguchi, H
AU  - Noguchi H
FAU - Nakao, K
AU  - Nakao K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int J Obes Relat Metab Disord
JT  - International journal of obesity and related metabolic disorders : journal of the 
      International Association for the Study of Obesity
JID - 9313169
RN  - 0 (Blood Glucose)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Insulin)
RN  - 0 (Leptin)
SB  - IM
MH  - Animals
MH  - Blood Glucose/analysis
MH  - Brain-Derived Neurotrophic Factor/*therapeutic use
MH  - Diabetes Mellitus/blood/*drug therapy
MH  - Drug Evaluation, Preclinical
MH  - Drug Resistance
MH  - Eating/drug effects
MH  - Glucose Tolerance Test
MH  - Insulin/blood
MH  - Leptin/*blood
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Obesity/blood/*drug therapy
EDAT- 2003/04/22 05:00
MHDA- 2003/05/20 05:00
CRDT- 2003/04/22 05:00
PHST- 2003/04/22 05:00 [pubmed]
PHST- 2003/05/20 05:00 [medline]
PHST- 2003/04/22 05:00 [entrez]
AID - 0802265 [pii]
AID - 10.1038/sj.ijo.0802265 [doi]
PST - ppublish
SO  - Int J Obes Relat Metab Disord. 2003 May;27(5):557-65. doi: 
      10.1038/sj.ijo.0802265.