RAPID REPORT: Dietary intervention prior to pregnancy reverses metabolic programming in male offspring of obese rats

Abstract

Obesity involving women of reproductive years is increasing dramatically in both developing and developed nations. Maternal obesity and accompanying high energy obesogenic dietary (MO) intake prior to and throughout pregnancy and lactation program offspring physiological systems predisposing to altered carbohydrate and lipid metabolism. Whether maternal obesity-induced programming outcomes are reversible by altered dietary intake commencing before conception remains an unanswered question of physiological and clinical importance. We induced pre-pregnancy maternal obesity by feeding female rats with a high fat diet from weaning to breeding 90 days later and through pregnancy and lactation. A dietary intervention group (DINT) of MO females was transferred to normal chow 1 month before mating. Controls received normal chow throughout. Male offspring were studied. Offspring birth weights were similar. At postnatal day 21 fat mass, serum triglycerides, leptin and insulin were elevated in MO offspring and were normalized by DINT. At postnatal day 120 serum glucose, insulin and homeostasis model assessment (HOMA) were increased in MO offspring; glucose was restored, and HOMA partially reversed to normal by DINT. At postnatal day 150 fat mass was increased in MO and partially reversed in DINT. At postnatal day 150, fat cell size was increased by MO. DINT partially reversed these differences in fat cell size. We believe this is the first study showing reversibility of adverse metabolic effects of maternal obesity on offspring metabolic phenotype, and that outcomes and reversibility vary by tissue affected.

Depot- and sex-specific effects of maternal obesity in offspring’s adipose tissue

“…weight gain, hormonal status, inflammation grade, and so on). It may also depend on the difference of genetic background of rat strain used (Wistar vs Sprague-Dawley) (Zambrano et al 2010). …”

Maternal over-nutrition and offspring obesity predisposition: targets for preventative interventions

“…Lower maternal plasma leptin levels have been reported in human mothers that report high levels of physical activity. 22 In addition, a recent rat study 54 reported that offspring of high-fat fed obese female rats that were switched to a control diet at 1 month before conception did not show an obese or insulin resistant phenotype at weaning compared with offspring of obese female rats maintained on the high-fat diet throughout pregnancy and lactation. Serum leptin levels reported at weaning, were similar between mothers in the dietary intervention group compared with controls fed chow throughout, and were significantly lower compared with the continual high-fat fed obese group.…”

Developmental programming of the metabolic syndrome - critical windows for intervention

“…These results demonstrated for the first time that direct manipulation of postnatal diet can limit adverse outcomes of developmental programming. Furthermore, work by Zambrano et al [162] has shown that dietary intervention (changing from an obesogenic HF diet to a normal chow diet) prior to pregnancy and lactation can reverse metabolic programming of male offspring of obese rats.…”