Gender difference in the effect of intrauterine malnutrition on the central anorexigenic action of insulin in adult rats.
OBJECTIVE
We evaluated whether insulin hypophagia and hypothalamic signaling are affected in adult rats exposed to intrauterine undernutrition.


METHODS
Pregnant rats ate ad libitum throughout pregnancy and lactation (control, C) or 50% of control intake in the first 2 wk of pregnancy (restricted, R). Four-month-old C and R progeny received insulin or vehicle intracerebroventricular injections for evaluation of 24-h food intake, hypothalamic insulin receptor (IR), and IR substrate-1 (IRS-1) protein content and tyrosine phosphorylation, pp185 phosphorylation, and IRS-1 association with phosphatidylinositol 3-kinase (PI3-K).


RESULTS
With respect to males, R males had normal body composition and insulin-induced hypophagia. IR protein levels were lower but IR phosphorylation was higher in R than in C males. IRS-1 levels and phosphorylation were similar between C and R males, insulin stimulated an IRS-1/PI3-K association in C but not in R males, and pp185 phosphorylation was higher in R than in C males. For females, body fat and serum leptin were elevated in R females. Insulin inhibited food intake in C but not in R females. Insulin-induced IR phosphorylation and protein levels of IR and IRS-1 were higher in R than in C females. However, IRS-1 and pp185 phosphorylation and IRS-1/PI3-K association were significantly stimulated by insulin in C but not in R females.


CONCLUSIONS
Female adult rats exposed to intrauterine undernutrition had increased adiposity, marked impairment of hypothalamic insulin signaling, and loss of insulin-induced hypophagia. These disturbances were less severe or even absent in male progeny. The findings show that female progeny are more susceptible than their male siblings to the effects of maternal malnutrition.
Sardinha
Fátima L C
FL
Department of Physiology, Division of Nutrition Physiology, Federal University of São Paulo-UNIFESP, São Paulo, Brazil.
Telles
Mônica M
MM
Albuquerque
Kelse T
KT
Oyama
Lila M
LM
Guimarães
Paulo A M P
PA
Santos
Oscar F P
OF
Ribeiro
Eliane B
EB
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001823:Body Composition / Q000502:physiology; D004038:Diet, Reducing; D004435:Eating / Q000502:physiology; D005260:Female; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology*; D007276:Injections, Intraventricular; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007774:Lactation / Q000502:physiology; D008297:Male; D044342:Malnutrition / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism / Q000502:physiology; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism*; D012737:Sex Factors; D015398:Signal Transduction / Q000502:physiology
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D011972:Receptor, Insulin