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Am J Physiol Regul Integr Comp Physiol (June 6, 2007). doi:10.1152/ajpregu.00117.2007
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Submitted on February 15, 2007
Accepted on June 5, 2007

Long-term consequences of maternal high-fat feeding on hypothalamic leptin sensitivity and diet-induced obesity in the offspring

Jacqueline Ferezou-Viala1*, Anne-france Roy2, Colette Serougne3, Daniel Gripois1, Michel Parquet1, Virginie Bailleux1, Arieh Gertler4, Bernadette Delplanque1, Jean Djiane1, Michel Riottot1, and Mohammed Taouis1

1 Neuroendocrinologie Moleculaire de la prise alimentaire, UNiversity Paris 11, ORSAY, France
2 Neuroendocrinologie Moleculaire de la prise alimentaire, UNiversity Paris 11, ORSAY, France; Neuroedocrinologie Moleculaire de la prise alimentaire, UNiversity Paris 11, ORSAY, France
3 Neuroedocrinologie Moleculaire de la prise alimentaire, UNiversity Paris 11, ORSAY, France; Neuroendocrinologie Moleculaire de la prise alimentaire, UNiversity Paris 11, ORSAY, France
4 Agriculture, The Hebrew University of Jerusalem, Rehovot, Israel

* To whom correspondence should be addressed. E-mail: jacqueline.ferezou{at}u-psud.fr.

Epidemiological studies suggest that the alteration of hormonal and metabolic environment during fetal and neonatal development contributes to development of metabolic syndrome in adulthood. Here, we investigate the impact of maternal high-fat (HF) diet on hypothalamic leptin sensitivity and body weight gain of offspring. Adult Wistar female rats received HF or control diet (C) diet for 6 weeks before gestation until the end of the suckling period. After weaning, pups received either C or HF diet during 6 weeks. Body weight gain, metabolic and endocrine parameters were measured in the 8 groups of rats formed according to post-weaning diet, maternal diet and gender. To evaluate hypothalamic leptin sensitivity in each group, STAT-3 phosphorylation was measured in response to leptin intraperitoneal bolus. Pups exhibited similar body weights at birth but at weaning, those born to HF dams weighed significantly less (-12%) than those born to C dams. Under HF diet, males and females born to HF dams exhibited smaller body weight and feed efficiency than those born to C dams, suggesting increased energy expenditure programmed by the maternal HF diet. Thus, maternal HF feeding could be protective against adverse effects of the HF diet as observed in male offspring of control dams: overweight (+17%) with hyperleptinemia and hyperinsulinemia. Furthermore, offspring of HF dams fed either C or HF diet exhibited an alteration in hypothalamic leptin-dependent STAT-3 phosphorylation. We conclude that maternal high-fat diet programs a hypothalamic leptin resistance in offspring which, however, fails to increase the body weight gain until adulthood.




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