Prenatal exposure to undernutrition and programming of responses to high-fat feeding in the rat

Abstract

Fetal undernutrition programmes risk of later metabolic disorders. Postnatal factors modify the programmed phenotype. This study aimed to assess the effects of a postnatal high-fat (HF) challenge on body weight gain, adiposity and gene expression following prenatal undernutrition. Pregnant rats were fed either a control diet or a low-protein (LP) diet, targeted at days 0–7 (LPE), days 8–14 (LPM), or days 15–22 (LPL) gestation. At 12 weeks of age offspring were either fed standard laboratory chow diet (4·13 % fat), or a 39·5 % fat diet, for 10 weeks. LP exposure had no effect on weight gain or abdominal fat in males. Females exposed to LP dietin uteroexhibited a similar weight gain on HF diet as on the chow diet. Programming of fat deposition was noted in LPE females and males of the LPM and LPL groups (P = 0·019). Hypothalamic expression of galanin mRNA was similar in all groups, but expression of the galanin-2 receptor was modified by LP exposure in female offspring. Hepatic expression of sterol response element binding protein (SREBP-1c) was decreased by LP at both the mRNA (P = 0·008) and protein (P < 0·001) level. HF feeding increased expression of SREBP-1c mRNA three-fold in controls, with little response noted in the LP groups. Interactions of factors such as postnatal diet, age and sex act together with prenatal factors to determine metabolic function and responsiveness at any stage of postnatal life. This study further establishes a role for prenatal nutrition in programming the genes involved in lipid metabolism and appetite regulation.