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Metabolic adaptations to early life protein restriction differ by offspring sex and post-weaning diet in the mouse
K W Whitaker1, K Totoki, T M Reyes
1Department of Pharmacology, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-5158, USA.
Insights
Low birth weight in mice, caused by maternal low protein diet, leads to metabolic changes. Offspring sex and diet after weaning significantly impact these adaptations, with females potentially more vulnerable to long-term health issues.
Area of Science:
- Developmental programming
- Metabolic adaptations
- Maternal nutrition
Background:
- Low birth weight (LBW) globally affects 1 in 7 infants.
- LBW predicts lifelong risks for cardiovascular disease, obesity, and diabetes.
- Maternal low protein diet is a known rat model for LBW and chronic disease risk.
Purpose of the Study:
- To establish and characterize a mouse model for LBW induced by maternal low protein diet.
- To investigate sex-specific metabolic adaptations in offspring.
- To explore the influence of post-weaning diet on metabolic outcomes.
Main Methods:
- Mice dams consumed a low protein (8%) diet during pregnancy and lactation.
- Offspring were assessed for metabolic parameters including food intake, activity, and glucose tolerance.
- Post-weaning diets included control or high-fat options.
Main Results:
- Significant sex differences in metabolic adaptations were observed.
- Male offspring on a high-fat diet showed increased food intake, hyperactivity, and metabolic rate.
- Female offspring consistently exhibited increased food intake and hypometabolism, irrespective of diet.
Conclusions:
- Offspring sex and post-weaning diet are critical determinants of metabolic adaptation to early life protein deficiency.
- Female offspring may face higher vulnerability to long-term adverse health consequences associated with LBW.
- This mouse model provides a platform for studying molecular mechanisms linking early life adversity to chronic disease.
Background And Aims:
Low birth weight affects 1 in every 7 babies born globally and can predict a lifetime of increased risk for adverse health outcomes, including cardiovascular disease, hypertension, obesity, diabetes, and metabolic syndrome. Maternal low protein diet during pregnancy and lactation is a well-characterized rat model for low birth weight and the subsequent increase in chronic disease risk. However, mice have been relatively understudied in this paradigm and represent a critical resource for investigating the underlying molecular mechanisms that link adverse early life experience and the development of chronic disease.
Methods And Results:
The present manuscript describes a mouse model of low birth weight (maternal consumption of low protein diet (8% protein) through pregnancy and lactation) and characterizes metabolic adaptations (food intake, locomotor activity, oxygen consumption, and glucose tolerance) in male and female offspring. At weaning, mice were maintained either on the control diet or a high fat diet. Notable sex differences were observed, with male mice from the low protein pregnancies showing increased food intake, hyperactivity and increased metabolic rate only when weaned to the high fat diet, while female mice consistently showed increased food intake and were hypometabolic, regardless of post-weaning diet.
Conclusion:
These data identify offspring sex and post-weaning diet as critical variables in the metabolic adaptations to early life protein deficiency, and suggest that females may be more vulnerable to the adverse long-term health consequences of low birth weight.
