title: Obesity-Associated Alterations in Glucose Metabolism Are Reversed by Chronic Bilateral Stimulation of the Abdominal Vagus Nerve.
abstract: Acute vagal stimulation modifies glucose and insulin metabolism, but the effect of chronic bilateral vagal stimulation is not known. Our aim was to quantify the changes in whole-body and organ-specific insulin sensitivities 12 weeks after permanent, bilateral, vagal stimulation performed at the abdominal level in adult mini-pigs. In 15 adult mini-pigs, stimulating electrodes were placed around the dorsal and ventral vagi using laparoscopy and connected to a dual-channel stimulator placed subcutaneously. Animals were divided into three groups based on stimulation and body weight (i.e., lean nonstimulated, obese nonstimulated, and obese stimulated). Twelve weeks after surgery, glucose uptake and insulin sensitivity were measured using positron emission tomography during an isoglycemic clamp. Mean whole-body insulin sensitivity was lower by 34% (P< 0.01) and the hepatic glucose uptake rate was lower by 33% (P< 0.01) in obese-nonstimulated mini-pigs but was no different in obese-stimulated compared with lean mini-pigs. An improvement in skeletal glucose uptake rate was also observed in obese-stimulated compared with obese-nonstimulated groups (P< 0.01). Vagal stimulation was associated with increased glucose metabolism in the cingulate and prefrontal brain areas. We conclude that chronic vagal stimulation improves insulin sensitivity substantially in diet-induced obesity by both peripheral and central mechanisms.
authors.affiliation: Ani-Scans, Department of Nutrition, French National Institute for Agricultural Research, Saint-Gilles, France charles-henri.malbert@inra.fr.
authors.forename: Charles-Henri
authors.identifier: 0000-0002-0665-4545
authors.initials: CH
authors.lastname: Malbert
authors.affiliation: Axonic, Vallauris Cedex, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Picq
authors.affiliation: Axonic, Vallauris Cedex, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Divoux
authors.affiliation: LivaNova, Sorin CRM SAS, Clamart, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Henry
authors.affiliation: Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
mesh_terms: D000005:Abdomen; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D007333:Insulin Resistance; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D049268:Positron-Emission Tomography; D013552:Swine; D013556:Swine, Miniature; D055536:Vagus Nerve Stimulation
chemical_list: D001786:Blood Glucose; D005947:Glucose