How maternal diet composition influences offspring appetite and metabolic health

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Feb 15 2024

In a recent study published in the journal Obesity, researchers evaluated the impact of maternal dietary protein and carbohydrate balance on offspring's appetite and metabolic health.

Background

Animals have nutrient-specific hunger mechanisms for both macronutrients and micronutrients. Protein prioritizing, regulating calorie intake more closely than non-protein consumption, is associated with the human obesity pandemic. Lean growth, reduced protein efficiency, senescence, insulin resistance, physiological adaptation to higher-protein diets, and genetic adaptation to ancestral high-protein diets all contribute to this problem. The impact of maternal macronutrient balance on offspring behavior and health is uncertain.

About the study

In the present study, researchers evaluated the impact of the maternal high-protein diet on offspring. They placed dams on LP or HP diets and their offspring on a food choice experiment post-weaning, subsequently constraining them to no-choice standard or Western diets (WD).

The researchers used C57BL6/Jarc mice for the experiments. They started 30 dams on the study diets at 11 weeks of age and continued them for four weeks before mating. They measured dam food consumption and body weights weekly, while 30 studs arriving at four weeks of age were housed separately outside the mating period to avoid fighting.

The team manufactured experimental diets as dry pellets, matched for minerals and vitamins. The LP diet had 10% protein, 20% fat, and 70% carbohydrate, while the HP diet had 35% protein, 20% fat, and 45% carbohydrate. The stud diets had 19% protein, 18% fat, and 63% carbohydrate, with a total calorie intake of 14 kJ/g. The team fed adult offspring two diets: the standard diet, comprising 19% protein, 18% fat, and 63% carbohydrate, with a total calorie intake of 14 kJ/g, and the WD, including 10% protein, 40% fat, and 50% carbohydrate, with a total net calorie intake of 17 kJ/g.

The team moved 15-week-old dams to breeding cages, pairing them with studs and mating for a week. Both diets yielded comparable breeding success. They housed the dams individually during gestation and measured body weight two times per week to identify pregnancies. At three weeks of weaning, they selected 64 female and male offspring from dam pools. They housed three to eight-week-pups individually, measuring body weight weekly.

The team performed a food preference experiment to evaluate the impact of maternal diets on offspring protein nutrient targets during intrauterine and early life. They conducted another choice testing round at week 40 to investigate whether the protein-based targets programmed during early life persist in the later stages. The team obtained murine blood at weeks 16 and 46 to perform oral glucose tolerance assessments and enzyme-linked immunosorbent assays (ELISA) to measure insulin levels. They also measured cholesterol, cortisone, liver function enzymes, triglycerides, and fibroblast growth factor 21 (FGF21) levels from murine sera obtained at week 46. They performed mixed-effects modeling to assess offspring data, including maternal and pup diets and gender as fixed-type effects.

Results

Offspring of high-protein diet-group dams showed higher protein consumption and body weight during early life than those of low-protein diet-group dams. The protein leverage concept, indicating that higher protein consumption targets led to higher food consumption among offspring fed no-choice diet types, resulting in higher fat mass and body weight, could predict the finding.

Dams remained on both diets throughout pregnancy and lactation, with body weights for both groups remaining similar in before-mating and initial gestational periods. However, dams fed high-protein diets were heavier in the end-gestational period to the initial 14 days of lactation, and body weights were similar towards the termination of the lactation period.

Pups from dams fed with high-protein diets ingested more protein and energy than those fed with low-protein diets for both females and males. HP targets in young murine animals were related to increased food consumption and body weights on fixed adult diets. Mice in WD had higher food intake regardless of dam diet, while standard mice showed a difference in food consumption, with pups of high-protein diet-group dams showing increased food intake compared to those of low-protein diet-group dams.

The study also found a significant three-way interaction between dam diet, pup diet, and gender in the serum biochemistry of offspring. Female offspring from high-protein diet-group dams had slightly higher FGF21 levels, while male offspring decreased with HP maternal diets at 46 weeks. Offspring from high-protein diet-group dams had increased energy expenditure in adulthood when fed a standard diet but decreased compared to maternal low-protein diet-fed groups when fed WD.

Conclusion

Overall, the study findings showed that high-protein maternal diets during preconception, pregnancy, and lactation lead to higher protein-based targets for offspring, affecting their metabolic health in later life. High-protein maternal diets combined with adult Western diets exacerbate obesity. High-protein maternal diets increase protein intake, increasing body mass and weight. In dams, an LP diet increased food consumption during gestation but caused no significant differences in body weight. Future research must elucidate the mechanisms underlying the programming persistence of maternally-induced phenotypes.