Abstract
Maternal obesity is associated with increased risk of pregnancy complications and greater risk of obesity in offspring, but studies designed to examine preconception weight loss are limited. The objective of this study was to determine if a combined dietary [oligofructose (OFS)] and pharmacological (sitagliptin) preconception intervention could mitigate poor pregnancy outcomes associated with maternal obesity and improve offspring metabolic health and gut microbiota composition. Diet-induced obese female Sprague-Dawley rats were randomized to one of four intervention groups for 8 weeks: (1) Obese-Control (consumed control diet during intervention); (2) Obese-OFS (10% OFS diet); (3) Obese-S (sitagliptin drug); (4) Obese-OFS + S (combination treatment). Two reference groups were also included: (5) Obese-HFS (untreated obese consumed high fat/sucrose diet throughout study); (6) Lean-Control (lean reference group that were never obese and consumed control diet throughout). Offspring consumed control diet until 11 weeks of age followed by HFS diet until 17 weeks of age. The Obese-OFS + S rats lost weight during the intervention phase whereas the OFS and S treatments attenuated weight gain compared with Obese-HFS (p < 0.05). Gestational weight gain was lowest in Obese-OFS + S rats and highest in Obese-HFS rats (p < 0.05). Prepregnancy intervention did not affect reproductive parameters but did affect pregnancy outcomes including litter size. Male Obese-OFS offspring had significantly lower percent body fat than Obese-HFS at 17 weeks. Female Obese-S and Obese-OFS offspring had significantly lower fasting glucose at 17 weeks compared with Obese-Control and Obese-HFS. Clostridium cluster XI was higher in Obese-HFS and Obese-S dams at birth compared with all other groups. Dams with an adverse pregnancy outcome had significantly lower (p = 0.035) Lactobacillus spp. compared with dams with normal or small litters. At weaning, male offspring of Obese-HFS had higher levels of Methanobrevibacter than all other groups except Obese-S and female Obese-HFS offspring had higher Enterobacteriaceae compared with all other groups. At 11 and 17 weeks of age, Bacteroides/Prevotella spp. was significantly lower in male and female offspring of Obese-HFS dams compared with all other groups except Obese-OFS + S. Modest weight loss induced with a diet-drug combination did not affect maternal fecundity but did have sex-specific effects on offspring adiposity and glycemia that may be linked to changes in offspring microbiota.
Highlights
Over the past 30 years, worldwide obesity has nearly doubled [1]
We have recently shown in rats that maternal prebiotic consumption during pregnancy and lactation normalized gestational weight gain, reduced offspring body fat and fasting glucose levels and increased Bifidobacterium spp. in both mothers and offspring [21]
There was a significant attenuation in weight gain in the ObeseOFS and Obese-S groups compared with Obese-high fat/sucrose (HFS)
Summary
Over the past 30 years, worldwide obesity has nearly doubled [1]. A marked increase in preconception body mass index (BMI) in women has occurred. A growing body of evidence suggests that increasing maternal BMI is associated with a decrease in fecundity [2, 3]. Impaired fecundity has been shown in diet-induced obese mice [4]. The Collaborative Perinatal Project (USA) found that the probability of conception is decreased by 18% in women with a BMI ≥ 30 and decreased 8% in women with a BMI between 25 and 29.9 kg/m2 compared with women who have a BMI between 18.5 and 24.9 kg/m2 [2]. The Danish National Birth Cohort study found that women with obesity are more likely to undergo infertility treatment than women with normal weight and to take longer than 1 year to conceive [5]
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