Maternal obesity is becoming more prevalent. We used borderline hypertensive rats (BHR) to investigate whether a high-fat diet at different stages of development has adverse programming consequences on metabolic parameters and blood pressure. Wistar dams were fed a high- or low-fat diet for 6 wk before mating with spontaneously hypertensive males and during the ensuing pregnancy. At birth, litters were fostered to a dam from the same diet group as during gestation or to the alternate diet condition. Female offspring were weaned on either control or “junk food” diets until about 6 mo of age. Rats fed the high-fat junk food diet were hyperphagic relative to their chow-fed controls. The junk food-fed rats were significantly heavier and had greater fat pad mass than those rats maintained on chow alone. Importantly, those rats suckled by high-fat dams had heavier fat pads than those suckled by control diet dams. Fasting serum leptin and insulin levels differed as a function of the gestational, lactational, and postweaning diet histories. Rats gestated in, or suckled by high-fat dams, or maintained on the junk food diet were hyperleptinemic compared with their respective controls. Indirect blood pressure did not differ as a function of postweaning diet, but rats gestated in the high-fat dams had lower mean arterial blood pressures than those gestated in the control diet dams. The postweaning dietary history affected food-motivated behavior; junk food-fed rats earned less food pellets on fixed (FR) and progressive (PR) ratio cost schedules than chow-fed controls. In conclusion, the effects of maternal high-fat diet during gestation or lactation were mostly small and transient. The postweaning effects of junk food diet were evident on the majority of the parameters measured, including body weight, fat pad mass, serum leptin and insulin levels, and operant performance.

Mice with homozygous genetic disruption of the melanocortin-4 receptor gene (MC4R−/−) are known to be hyperphagic and become obese, while those with disruption of the melanocortin-3 receptor gene (MC3R−/−) do not become markedly obese. The contribution of MC3R signaling in energy homeostasis remains little studied. In the present work, we compare MC3R−/− mice with wild-type (WT), MC4R−/−, and mice bearing disruption of both genes (double knockout, DKO) on select feeding and neuroanatomical dimensions. DKO mice were significantly more obese than MC4R−/−, whereas MC3R−/− weighed the same as WT. In a food demand protocol, DKO and MC4R−/− were hyperphagic at low unit costs for food, due primarily to increased meal size. However, at higher costs, their intake dropped below that of WT and MC3R−/−, indicating increased elasticity of food demand. To determine whether this higher elasticity was due to either the genotype or to the obese phenotype, the same food demand protocol was conducted in dietary obese C57BL6 mice. They showed similar elasticity to lean mice, suggesting that the effect is of genotypic origin. To assess whether the increased meal size in MC4R−/− and DKO might be due to reduced CCK signaling, we examined the acute anorectic effect of peripherally administered CCK and subsequently the induction of c-Fos immunoreactivity in select brain regions. The anorectic effect of CCK was comparable in MC4R−/− , DKO, and WT, but it was unexpectedly absent in MC3R−/−. CCK-induced c-Fos was lower in the paraventricular nucleus in MC3R−/− than the other genotypes. These data are discussed in terms of demand functions for food intake, MC receptors involved in feeding, and their relation to actions of gut hormones, such as CCK, and to obesity.