PMID- 12746306
OWN - NLM
STAT- MEDLINE
DCOM- 20030625
LR  - 20111117
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 144
IP  - 6
DP  - 2003 Jun
TI  - Reversal of behavioral and metabolic abnormalities, and insulin resistance 
      syndrome, by dietary restriction in mice deficient in brain-derived neurotrophic 
      factor.
PG  - 2446-53
AB  - Dietary restriction (DR) extends life span and improves glucose metabolism in 
      mammals. Recent studies have shown that DR stimulates the production of 
      brain-derived neurotrophic factor (BDNF) in brain cells, which may mediate 
      neuroprotective and neurogenic actions of DR. Other studies have suggested a role 
      for central BDNF signaling in the regulation of glucose metabolism and body 
      weight. BDNF heterozygous knockout (BDNF+/-) mice are obese and exhibit features 
      of insulin resistance. We now report that an intermittent fasting DR regimen 
      reverses several abnormal phenotypes of BDNF(+/-) mice including obesity, 
      hyperphagia, and increased locomotor activity. DR increases BDNF levels in the 
      brains of BDNF(+/-) mice to the level of wild-type mice fed ad libitum. BDNF(+/-) 
      mice exhibit an insulin-resistance syndrome phenotype characterized by elevated 
      levels of circulating glucose, insulin, and leptin; DR reduces levels of each of 
      these three factors. DR normalizes blood glucose responses in glucose tolerance 
      and insulin tolerance tests in the BDNF(+/-) mice. These findings suggest that 
      BDNF is a major regulator of energy metabolism and that beneficial effects of DR 
      on glucose metabolism are mediated, in part, by BDNF signaling. Dietary and 
      pharmacological manipulations of BDNF signaling may prove useful in the 
      prevention and treatment of obesity and insulin resistance syndrome-related 
      diseases.
FAU - Duan, Wenzhen
AU  - Duan W
AD  - Laboratory of Neurosciences, National Institute on Aging Gerontology Research 
      Center, Baltimore, Maryland 21224, USA.
FAU - Guo, Zhihong
AU  - Guo Z
FAU - Jiang, Haiyang
AU  - Jiang H
FAU - Ware, Melvin
AU  - Ware M
FAU - Mattson, Mark P
AU  - Mattson MP
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Blood Glucose)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Insulin)
RN  - 0 (Leptin)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Animals
MH  - Blood Glucose
MH  - Brain Chemistry/genetics
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - *Caloric Restriction
MH  - Hyperinsulinism/diet therapy/physiopathology
MH  - Hyperphagia/diet therapy/physiopathology
MH  - Insulin/blood
MH  - *Insulin Resistance
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Leptin/blood
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Motor Activity
MH  - Obesity/*diet therapy/*physiopathology
MH  - Phenotype
MH  - Signal Transduction/physiology
EDAT- 2003/05/15 05:00
MHDA- 2003/06/26 05:00
CRDT- 2003/05/15 05:00
PHST- 2003/05/15 05:00 [pubmed]
PHST- 2003/06/26 05:00 [medline]
PHST- 2003/05/15 05:00 [entrez]
AID - 10.1210/en.2002-0113 [doi]
PST - ppublish
SO  - Endocrinology. 2003 Jun;144(6):2446-53. doi: 10.1210/en.2002-0113.