Impact of long-term maternal high-fat, high-sugar feeding on gastric vagal afferent responses and feeding behaviour in mouse offspring.

Poor maternal nutrition and excessive gestational weight gain predict future development of obesity in offspring. Preclinically, maternal obesity induced by a high-fat, high-sugar diet (HFHSD) induces hyperphagia and obesity in offspring. We hypothesized that this might, in part, reflect reduced peripheral gastric vagal afferent (GVA) satiety signalling. Female Glu Venus mice were fed a standard laboratory diet (SLD) or HFHSD for 11 weeks before mating and throughout pregnancy and lactation. Offspring were weaned onto a SLD, then housed in metabolic cages at 6-7 weeks old to assess feeding behaviour. In vitro single-fibre GVA recordings were conducted on tissue collected from 8-week-old mice. Before mating, HFHSD dams were 13% heavier, with 66% higher relative fat mass compared with SLD dams. Maternal diet had no impact on total food intake or offspring weight. Meal size during the light phase was 14% larger in HFHSD than control offspring. Meal duration was longer in HFHSD than control offspring of both sexes across 24 h and the dark phase, and in females during the light phase. HFHSD offspring ate fewer meals than control offspring across all time periods. Tension-sensitive GVAs responded less to stretch in male, but not female, HFHSD than SLD offspring. Mucosal GVA responses to mucosal stroking were unaffected by maternal diet or offspring sex. In conclusion, exposure in utero and during lactation to elevated maternal adiposity and maternal HFHSD consumption induces male-specific programming of reduced GVA responses to stretch. Meal size was increased in both sexes only during the light phase, suggesting programming of other appetite-regulatory pathways by this exposure.