Moderate Caloric Restriction in Lactating Rats Protects Offspring against Obesity and Insulin Resistance in Later Life

Abstract

We aimed to assess the lasting effects of caloric restriction in lactating rats on body weight and insulin sensitivity of their offspring. Dams were fed with either ad libitum standard diet or a 30% caloric restricted diet throughout lactation. After weaning, the offspring were fed with a normal-fat diet until the age of 15 wk, and then with a normal- or a high-fat (HF) diet until the age of 26 wk. Blood parameters were measured during ad libitum feeding conditions and after 14-h fasting. Food preferences were also measured. In dams, milk leptin concentration and leptin mRNA and protein levels in mammary gland were also determined. Caloric restricted dams showed higher mRNA and protein levels of leptin in mammary gland than controls, without significant changes in milk leptin concentration. The offspring of caloric restricted dams (CR) ate fewer calories and showed lower body weight gain and fat accumulation under the HF diet than their controls. CR also maintained unchanged circulating leptin levels under HF diet, whereas levels increased in controls. In addition, male CR were resistant to the increase of circulating triglycerides and of the homeostatic model assessment for insulin resistance produced in male controls under HF diet feeding; CR were also protected against the increased preference for fat-food occurring in females upon HF diet. These results suggest moderate caloric restriction during lactation protects from obesity development in offspring in adult life and from the related metabolic alterations, particularly dyslipidemia, insulin resistance, and hyperleptinemia, associated with HF diet feeding.

Moderate caloric restriction in lactating rats programs their offspring for a better response to HF diet feeding in a sex-dependent manner

“…In accordance with our previous results in the same cohort of animals at younger ages [25], we also show here that the offspring of caloric restricted dams during the suckling period display lower body weight and lower fat content in adulthood, compared with their controls, the difference being more patent when animals are exposed to the challenge of HF diet feeding. The lower body weight can be explained, at least in part, by lower food intake.…”

“…We previously described that a moderate caloric restriction (30%) in lactating dams confers certain protection against obesity development and from related metabolic alterations in adult life, particularly insulin resistance and hyperleptinemia [25]. However, little is known about the mechanisms that underlie these alterations and whether they are associated with changes in the expression of key genes involved in energy homeostasis.…”

“…At day 1 after delivery, excess pups in each litter were removed in order to keep 10 pups per dam (five males and five females, when possible) and dams were assigned to either control or caloric restricted group (n=6 in each group). The control group was fed ad libitum with standard diet, while the caloric restricted group was provided daily with a 30% caloric restricted diet throughout lactation, starting on day 1 after delivery and ending at weaning (day 21) as previously described [25]. After weaning, 36 animals from control dams (controls) (18 males and 18 females) and 36 from caloric restricted dams (CR) (18 males and 18 females) were placed two per cage, paired with another animal of the same group, and fed with standard diet until the age of 15 weeks; then they were distributed into two groups; normal fat (NF) group [animals (n=6/ group) continued with standard diet (2.9% calories from fat)] and high-fat (HF) group [animals (n=12/group) fed with a chow diet (4.7 kcal/g) with 45% calories from fat (Research Diets, NJ, USA)].…”

“…Other models of energy restriction obtained by severe food restriction in lactating dams [22] or by increasing the litter size [23,24] have also been associated with lower body weight and lower food intake in their adult offspring. In this sense, we have also recently described in rats that moderate caloric restriction (30%) in lactating dams protects their offspring against obesity as well as against insulin resistance in adulthood [25]. Most of these studies analyzing the lasting effects of maternal caloric restriction in offspring have mainly focused on the changes in body weight, food intake and/or circulating hormone levels [24,[26][27][28].…”

Nutritional Challenges and Opportunities during the Weaning Period and in Young Childhood

“…Similarly, moderate energy restriction during lactation has been shown to protect against enhanced adult fat accumulation in rats, whereas energy restriction during gestation has had the opposite effect [89]. These observations illustrate that growth depends on different fuels in fetal and postnatal life and is related to the timing of the development of individual organs and their nutritional needs during these different stages.…”