PMID- 25054843
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140729
LR  - 20140724
IS  - 2040-1752 (Electronic)
IS  - 2040-1744 (Linking)
VI  - 4
IP  - 3
DP  - 2013 Jun
TI  - Mechanism of programmed obesity: altered central insulin sensitivity in 
      growth-restricted juvenile female rats.
PG  - 239-48
LID - 10.1017/S2040174413000019 [doi]
AB  - Intrauterine growth-restricted (IUGR) offspring are at increased risk of adult 
      obesity, as a result of changes in energy balance mechanisms. We hypothesized 
      that impairment of hypothalamic insulin signaling contributes to hyperphagia in 
      IUGR offspring. Study pregnant dams were 50% food restricted from days 10 to 21 
      to create IUGR newborns. At 5 weeks of age, food intake was measured following 
      intracerebroventricular (icv) injection of vehicle or insulin (10 mU) in control 
      and IUGR pups. At 6 weeks of age, with pups in fed or fasted (48 h) states, pups 
      received icv vehicle or insulin after which they were decapitated, and 
      hypothalamic arcuate (ARC) nucleus dissected for RNA and protein expression. IUGR 
      rats consumed more food than controls under basal conditions, consistent with 
      upregulated ARC phospho AMP-activated protein kinase (pAMPK) and neuropeptide Y 
      (NPY). Insulin acutely reduced food intake in both control and IUGR rats. 
      Consistent with anorexigenic stimulation, central insulin decreased AMP-activated 
      protein kinase and NPY mRNA expression and increased proopiomelanocortin mRNA 
      expression and pAkt, with significantly reduced responses in IUGR as compared 
      with controls. Despite feeding, IUGR offspring exhibit a persistent state of 
      orexigenic stimulation in the ARC nucleus and relative resistance to the 
      anorexigenic effects of icv insulin. These results suggest that impaired insulin 
      signaling contributes to hyperphagia and obesity in IUGR offspring.
FAU - Fukami, T
AU  - Fukami T
AD  - 1 Department of Obstetrics and Gynecology, Los Angeles Biomedical Research 
      Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
FAU - Sun, X
AU  - Sun X
AD  - 1 Department of Obstetrics and Gynecology, Los Angeles Biomedical Research 
      Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
FAU - Li, T
AU  - Li T
AD  - 1 Department of Obstetrics and Gynecology, Los Angeles Biomedical Research 
      Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
FAU - Yamada, M
AU  - Yamada M
AD  - 1 Department of Obstetrics and Gynecology, Los Angeles Biomedical Research 
      Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
FAU - Desai, M
AU  - Desai M
AD  - 1 Department of Obstetrics and Gynecology, Los Angeles Biomedical Research 
      Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
FAU - Ross, M G
AU  - Ross MG
AD  - 1 Department of Obstetrics and Gynecology, Los Angeles Biomedical Research 
      Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Dev Orig Health Dis
JT  - Journal of developmental origins of health and disease
JID - 101517692
EDAT- 2014/07/24 06:00
MHDA- 2014/07/24 06:01
CRDT- 2014/07/24 06:00
PHST- 2014/07/24 06:00 [entrez]
PHST- 2014/07/24 06:00 [pubmed]
PHST- 2014/07/24 06:01 [medline]
AID - S2040174413000019 [pii]
AID - 10.1017/S2040174413000019 [doi]
PST - ppublish
SO  - J Dev Orig Health Dis. 2013 Jun;4(3):239-48. doi: 10.1017/S2040174413000019.