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Updated: Apr 26, 2026
Fat Preference: A Novel Model of Eating Behavior in Rats
Published on: June 27, 2014
Mechanism of programmed obesity: altered central insulin sensitivity in growth-restricted juvenile female rats
11 Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
Insights
Intrauterine growth restriction (IUGR) in offspring leads to increased obesity risk due to impaired hypothalamic insulin signaling, causing overeating and resistance to appetite-regulating hormones.
Area of Science:
- Neuroendocrinology
- Metabolic Research
- Developmental Biology
Background:
- Intrauterine growth-restricted (IUGR) offspring face higher risks of adult obesity.
- Altered energy balance mechanisms are implicated in IUGR-related obesity.
- Hypothesized link between impaired hypothalamic insulin signaling and hyperphagia in IUGR.
Purpose of the Study:
- To investigate the role of hypothalamic insulin signaling in hyperphagia among IUGR offspring.
- To determine if impaired insulin action in the arcuate nucleus (ARC) contributes to overeating in IUGR.
Main Methods:
- IUGR model created by maternal food restriction in rats.
- Intracerebroventricular (icv) insulin injections administered to assess food intake and hypothalamic gene/protein expression.
- Analysis of ARC nucleus for key signaling molecules (pAMPK, NPY, POMC, pAkt) in fed and fasted states.
Main Results:
- IUGR rats exhibited increased basal food intake and upregulated orexigenic signals (pAMPK, NPY) in the ARC.
- Central insulin administration reduced food intake and modulated ARC neuropeptide expression in both groups.
- IUGR offspring showed blunted responses to insulin's anorexigenic effects, indicating relative insulin resistance in the hypothalamus.
Conclusions:
- IUGR offspring maintain a state of orexigenic stimulation in the ARC nucleus.
- Impaired hypothalamic insulin signaling contributes significantly to hyperphagia and subsequent obesity in IUGR individuals.
- Targeting hypothalamic insulin pathways may offer therapeutic strategies for managing obesity in IUGR populations.
Abstract:
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.
