A low maternal protein diet during pregnancy and lactation has sex‐ and window of exposure‐specific effects on offspring growth and food intake, glucose metabolism and serum leptin in the rat

Abstract

Extensive epidemiological and experimental evidence indicates that a sub-optimal environment during fetal and neonatal development in both humans and animals may programme offspring susceptibility to later development of chronic diseases including obesity and diabetes that are the result of altered carbohydrate metabolism. We determined the effects of protein restriction during pregnancy and/or lactation on growth, serum leptin, and glucose and insulin responses to a glucose tolerance test in male and female offspring at 110 days postnatal life. We fed Wistar rats a normal control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. Female but not male R pups weighed less than C at birth. After delivery, mothers received the C or R diet during lactation to provide four offspring groups: CC (first letter maternal pregnancy diet and second maternal lactation diet), RR, CR and RC. All offspring were fed ad libitum with C diet after weaning. Relative food intake correlated inversely with weight. Offspring serum leptin correlated with body weight and relative, but not absolute, food intake in both male and female pups. Serum leptin was reduced in RR female pups compared with CC and increased in RC males compared with CC at 110 days of age. Offspring underwent a glucose tolerance test (GTT) at 110 days postnatal life. Female RR and CR offspring showed a lower insulin to glucose ratio than CC. At 110 days of age male RR and CR also showed some evidence of increased insulin sensitivity. Male but not female RC offspring showed evidence of insulin resistance compared with CC. Cholesterol was similar and triglycerides (TG) higher in male compared with female CC. Cholesterol and TG were higher in males than females in RR, CR and RC (P < 0.05). Cholesterol and TG did not differ between groups in females. Cholesterol and TG were elevated in RC compared with CC males. Nutrient restriction in lactation increased relative whole protein and decreased whole lipid in both males and females. RC females showed decreased relative levels of protein and increased fat. We conclude that maternal protein restriction during either pregnancy and/or lactation alters postnatal growth, appetitive behaviour, leptin physiology, TG and cholesterol concentrations and modifies glucose metabolism and insulin resistance in a sexand time window of exposure-specific manner.

Established diet-induced obesity in female rats leads to offspring hyperphagia, adiposity and insulin resistance

“…Sex-related differences are commonly described in other models although no mechanism has been identified [47,48]. However, the design of our study in this regard was not ideal, as, for practical reasons, female offspring were studied at a younger age (8-9 months) than the males (10-11) months.…”

Group housing during gestation affects the behaviour of sows and the physiological indices of offspring at weaning

“…In recent years, a number of epidemiological and experimental studies have demonstrated that environmental factors exerting their influence during embryonic development may have the potential to induce a variety of metabolic changes later in life (Petry and Hales, 2000;Zambrano et al, 2006). Concerning the influence of the housing system during gestation on the offspring growth, Sorrells et al (2006) found that there were no significant differences in plasma tumour necrosis factor, α1-acid glycoprotein, haptoglobin and IgG concentrations in piglets from gilts housed individually or in groups during gestation.…”

Perinatal nutrient restriction induces long-lasting alterations in the circadian expression pattern of genes regulating food intake and energy metabolism

“…Many epidemiological studies have indeed demonstrated that infants born small for gestational age are more prone to develop obesity, hypertension and type 2 diabetes in adulthood. [27][28][29] Experimental studies have further corroborated that rodents and other animal species submitted to protein or calorie restriction during gestation and/or suckling exhibit hyperphagia, [30][31][32][33] insulin resistance, 34,35 reduced leptin sensitivity, 36,37 hepatic steatosis, 38 elevated blood pressure 39,40 and hyperlipidemia. 35,37,38 These observations have been explained by the thrifty phenotype hypothesis, also called metabolic programming or the developmental origins of disease.…”