Altered gastric vagal mechanosensitivity in diet-induced obesity persists on return to normal chow and is accompanied by increased food intake

• Published in: International Journal of Obesity Vol. 38; no. 5; pp. 636 - 642
• Main Authors: Kentish, S J, O'Donnell, T A, Frisby, C L, Li, H, Wittert, G A, Page, A J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2014; Nature Publishing Group
• Subjects: 631/443/319/367; 692/699/1702/393; Afferent Pathways - metabolism; Animals; Biological and medical sciences; Body fat; Body Weight; Body weight loss; Diet; Diet, High-Fat; Energy consumption; Energy Intake; Epidemiology; Epithelial cells; Epithelium; Esophagus; Feeding Behavior; Female; Food; Food consumption; Food intake; Gastric Mucosa - metabolism; Gene expression; Health aspects; Health Promotion and Disease Prevention; High fat diet; Immunohistochemistry; Insulin; Internal Medicine; Ketogenic diet; Laboratories; Leptin - secretion; Mechanical stimuli; Medical research; Medical sciences; Medicine; Medicine & Public Health; Medicine, Experimental; Metabolic Diseases; Mice; Mice, Inbred C57BL; mRNA; Mucosa; Obesity; Obesity - metabolism; original-article; Physiological aspects; Public Health; Real-Time Polymerase Chain Reaction; Receptors; Receptors, Leptin - metabolism; Satiety; Sensory neurons; Stimuli; Stomach; Tension; Thinness - metabolism; Vagus nerve; Vagus Nerve - metabolism; Weight control; Weight Gain; Weight loss; Australia; leptin; high fat diet; vagal afferents; Stomach; Obesity; Nutrition; Digestive system; Nutrition disorder; Metabolic diseases; Adipokine; Normal; Feeding; Diet; Food intake; Leptin; Fat; Nutritional status
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2013.138

Background and aims:
Gastric vagal afferents convey satiety signals in response to mechanical stimuli. The sensitivity of these afferents is decreased in diet-induced obesity. Leptin, secreted from gastric epithelial cells, potentiates the response of vagal afferents to mechanical stimuli in lean mice, but has an inhibitory effect in high-fat diet (HFD)-induced obese mice. We sought to determine whether changes in vagal afferent function and response to leptin in obesity were reversible by returning obese mice consuming a HFD to standard laboratory chow diet (SLD).
Methods:
Eight-week-old female C57BL/6 mice were either fed a SLD (
N
=20) or HFD (
N
=20) for 24 weeks. A third group was fed a HFD for 12 weeks and then a SLD for a further 12 weeks (RFD,
N
=18). An
in vitro
gastro-oesophageal vagal afferent preparation was used to determine the mechanosensitivity of gastric vagal afferents and the modulatory effect of leptin (0.1–10 n
M
) was examined. Retrograde tracing and quantitative RT–PCR were used to determine the expression of leptin receptor (LepR) messenger RNA (mRNA) in whole nodose and specific cell bodies traced from the stomach.
Results:
After 24 weeks, both the HFD and RFD mice had increased body weight, gonadal fat mass, plasma leptin, plasma insulin and daily energy consumption compared with the SLD mice. The HFD and RFD mice had reduced tension receptor mechanosensitivity and leptin further inhibited responses to tension in HFD, RFD but not SLD mice. Mucosal receptors from both the SLD and RFD mice were potentiated by leptin, an effect not seen in HFD mice. LepR expression was unchanged in the whole nodose, but was reduced in the mucosal afferents of the HFD and RFD mice.
Conclusion:
Disruption of gastric vagal afferent function by HFD-induced obesity is only partially reversible by dietary change, which provides a potential mechanism preventing maintenance of weight loss.