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

Abstract

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.