Using a diet and drug combination treatment prior to pregnancy to improve maternal health in rats

Abstract

Maternal obesity, before and during pregnancy, can program obesity risk in offspring. Glucagon‐like peptide‐1 (GLP‐1) is a satiety hormone stimulated by the prebiotic fiber, oligofructose (OFS). GLP‐1 is protected against degradation by the diabetes drug, sitagliptin. Our objective was to determine if treating maternal obesity in the pre‐pregnancy period with OFS and sitagliptin is more effective at reducing adiposity and improving gut microbiota profiles than either alone. Obese female rats (n=52) were randomized to 1 of 4 treatments for 8wk: 1) AIN‐93M; 2) OFS; 3) AIN‐93M+Sitagliptin; 4) OFS+ Sitagliptin. Reference groups were: high fat, sucrose (HFS, obese control), lean control, and caloric restriction (matched weight to gp 4). Rats were mated following treatment. Results showed: 1) Consumption of the HFS diet throughout pregnancy and lactation deteriorated maternal health with significantly increased adiposity and impaired glucose tolerance (P<0.05). 2) Whereas pre‐treating obesity with OFS and sitagliptin reduced maternal weight gain during pregnancy, rats that were calorically restricted showed excessive gestational weight gain. 3) The beneficial effects of OFS consumption on bifidobacteria and C. leptum numbers persisted throughout pregnancy and lactation. The significance of this work lies in identification of novel obesity treatments that could be used prior to conception and reduce the transmission of obesity risk to offspring. Funded by CIHR.