Fetal programming of metabolic health through a combined dietary and pharmacological pre‐pregnancy intervention in rats

Abstract

Maternal obesity is associated with low birth weight, type 2 diabetes and obesity risk in offspring. Diets high in oligofructose (OFS) improve glucose control through glucagon‐like‐peptide‐1 (GLP‐1). Sitagliptin inhibits the degradation of GLP‐1in vivo. The aim of this study was to determine if a combined OFS and sitagliptin pre‐pregnancy intervention in obese female Sprague‐Dawley rats can improve the metabolic health of female offspring. Obese female Sprague‐Dawley rats were randomized to 1 of 6 groups: 1) AIN‐93; 2) 10% OFS; 3) Sitagliptin; 4) AIN‐93+OFS+Sitagliptin; 5) High fat & sucrose (HFS); 6) Caloric restriction (CR). A lean reference group was also included. Pups consumed AIN‐93 until 11wk when they were given HFS diet for 6 wk. Body weight and blood glucose were assessed. At birth the offspring of combination‐treated dams were significantly heavier than offspring in all other groups (p<0.04). Following the HFS diet challenge the blood glucose area under the curve for offspring of the combination group was less than the HFS and CR groups (p<0.05). Despite higher birth weight, the combined treatment significantly improved offspring glycemic control in adulthood. Funded by CIHR and ACHRI.Grant Funding Source: CIHR and ACHRI