Pregnancy and a high‐fat, high‐sugar diet each attenuate mechanosensitivity of murine gastric vagal afferents, with no additive effects

Gastric vagal afferents (GVAs) sense food-related mechanical stimuli and signal to the CNS to initiate meal termination. Pregnancy and diet-induced obesity are independently associated with dampened GVA mechanosensitivity and increased food intake. Whether a high-fat, high-sugar diet (HFHSD) impacts pregnancy-related adaptations in GVA signalling is unknown and was investigated in this study. Three-week-old female Glu Venus-expressing mice, on a C57BL/6 background, were fed standard laboratory diet (SLD) or HFHSD for 12 weeks, and then half of each group were mated to generate late pregnant (Day 17.5; P-SLD N = 12, P-HFHSD N = 14) or non-pregnant (NP-SLD N = 12, NP-HFHSD N = 16) groups. Body weight and food intake were monitored in Promethion metabolic cages from before mating until Day 17.5 of pregnancy or equivalent ages in non-pregnant mice, prior to tissue collection at 07.00 h for in vitro single fibre GVA recording and gene expression analysis. Pregnant mice gained more weight than non-pregnant mice but weight gain was unaffected by diet. By mid-pregnancy, light-phase food intake (kJ and g) was higher in pregnant than in non-pregnant mice (each P < 0.001) due to larger meals (kJ and g, each P < 0.001), irrespective of diet. Pregnancy and HFHSD-feeding reduced tension-sensitive GVA mechanosensitivity (each P < 0.01), but pregnancy did not further downregulate GVA stretch responses within HFHSD mice (P = 0.652). Nodose ganglia growth hormone receptor mRNA abundance was upregulated in pregnancy, possibly contributing to lower GVA mechanosensitivity during pregnancy in SLD mice. Larger light-phase meals in pregnant compared to non-pregnant HFHSD mice may therefore reflect the downregulation of other satiety pathways. KEY POINTS: Gastric vagal afferents (GVAs) regulate food intake by sensing the arrival and quantity of food and communicating this information to the brain. In standard laboratory diet (SLD) mice, gastric tension-sensitive vagal afferent mechanosensitivity was attenuated in pregnant compared to non-pregnant mice, which is concurrent with increases in total food intake and meal size. Nodose ganglia growth hormone receptor mRNA abundance was increased in pregnancy, possibly accounting for attenuated GVA mechanosensitivity in pregnant SLD mice. In non-pregnant mice, tension-sensitive GVA mechanosensitivity was selectively attenuated in high-fat, high-sugar diet (HFHSD) compared to SLD mice. Despite this, HFHSD mice ate less food and smaller meals compared to the SLD mice, suggesting other satiety mechanisms are limiting food intake. Despite higher food intake, there was no further reduction in mechanosensitivity in pregnant HFHSD mice compared to non-pregnant HFHSD mice and further studies are required to increase understanding of food intake regulation across pregnancy.