Nesfatin-1 modulates murine gastric vagal afferent mechanosensitivity in a nutritional state dependent manner

•Nesfatin-1 potentiated mucosal receptor mechanosensitivity in lean fed and fasted but not high fat diet (HFD) mice.•Tension receptor mechanosensitivity was unaffected by nesfatin-1 in lean fed or fasted mice, but inhibited in HFD mice.•Plasma concentrations of nesfatin-1were unchanged between fed, fasted and HFD mice.•No difference in NUCB2 mRNA expression was observed in gastric mucosa or gonadal fat of fed, fasted and HFD mice.•Nesfatin-1 modulated gastric vagal afferents in a nutritional state dependent manner. Food intake is regulated by vagal afferent signals from the stomach. Nesfatin-1 is an anorexigenic peptide produced within the gastrointestinal tract and has well defined central effects. We aimed to determine if nesfatin-1 can modulate gastric vagal afferent signals in the periphery and further whether this is altered in different nutritional states. Female C57BL/6J mice were fed either a standard laboratory diet (SLD) or a high fat diet (HFD) for 12 weeks or fasted overnight. Plasma nucleobindin-2 (NUCB2; nesfatin-1 precursor)/nesfatin-1 levels were assayed, the expression of NUCB2 in the gastric mucosa and adipose tissue was assessed using real-time quantitative reverse-transcription polymerase chain reaction. An in vitro preparation was used to determine the effect of nesfatin-1 on gastric vagal afferent mechanosensitivity. HFD mice exhibited an increased body weight and adiposity. Plasma NUCB2/nesfatin-1 levels were unchanged between any of the groups of mice. NUCB2 mRNA was detected in the gastric mucosa and gonadal fat of SLD, HFD and fasted mice with no difference in mRNA abundance between groups in either tissue. In SLD and fasted mice nesfatin-1 potentiated mucosal receptor mechanosensitivity, an effect not observed in HFD mice. Tension receptor mechanosensitivity was unaffected by nesfatin-1 in SLD and fasted mice, but was inhibited in HFD mice. In conclusion, Nesfatin-1 modulates gastric vagal afferent mechanosensitivity in a nutritional state dependent manner.