Longitudinal 1H NMR Metabolomics Analysis Identifies Differences in Maternal Response to Pregnancy and Lactation between Lean and Diet‐Induced Obese Sprague‐Dawley Rats
Authors: Paul Heather A , Bomhof Marc R , Vogel Hans J , Reimer Raylene A 
Published: November 2023

Maternal obesity adversely affects both maternal and offspring health and increases the risk of metabolic disease in offspring in later life. However, how lean versus obese mothers differ in their metabolic response to pregnancy and lactation and their significance in the context of programming of offspring metabolic disease remains to be determined. Here, using an animal model of maternal obesity, we sought to identify the longitudinal metabolic changes characterizing obese versus lean pregnant and lactating dams in order to identify key differences in how obese and lean dams respond to pregnancy and lactation and the potential impact on offspring metabolic health.

Obesity was induced in female Sprague‐Dawley rats over 10 weeks using a high‐fat/sucrose diet. A lean control group was maintained on a standard AIN‐93 diet throughout the study. Diet‐induced obese and lean female Sprague‐Dawley rats were bred and maintained on their respective diets throughout gestation and lactation. At parturition, litters were culled to 10 pups. The study concluded at weaning of the pups. Metabolites in maternal serum collected pre‐pregnancy, on gestation day 14, and lactation day 19 were measured and quantified using proton nuclear magnetic resonance (1H NMR) spectroscopy and analyzed using both univariate and multivariate statistical analysis. Maternal body weight, food intake, glycaemia, insulinaemia, and body composition was assessed. Pup body weight and body composition was also measured.

Obese females were heavier than lean females throughout the study (p<0.05). Obese dams had higher caloric intake during gestation (p<0.05) but not lactation, and had higher fat weight and percent body fat at weaning (p<0.05). No differences in glycaemia and insulinaemia were detected during either pregnancy or lactation. Pups of obese dams weighed more by lactation day 7, remained heavier until weaning, and had higher percent body fat at weaning (p<0.05). Results indicate that though some overlap exists with respect to metabolic changes that occur as dams become pregnant and transition to lactation, some key differences are present. For example, when comparing changes in circulating levels of ketone bodies (beta‐hydroxybutyrate, acetate, acetoacetate) from pre‐pregnancy to gestation, the significance of the difference was higher in lean dams (p<1×10−5) compared to obese dams (p<0.01), which contributed to a higher degree of similarity between pre‐pregnancy and gestational metabolic profiles in obese dams (R2=0.709, Q2=0.541) compared to lean dams (R2=0.889, Q2=0.847).

In summary, longitudinal 1H NMR metabolomics is a valuable tool in revealing key differences in metabolic adaptations to pregnancy and lactation between lean and obese dams that has the potential to improve understanding of the increased risk of adverse outcomes in mothers with obesity and their offspring.

Support or Funding Information

Funded by AIHS, NSERC, and CIHR