Obesity-associated alterations in glucose metabolism are reversed by chronic bilateral stimulation of the abdominal vagus nerve
2017
Malbert, Charles-Henri | Picq, Chloé | Divoux, Jean-Louis | Henry, Christine | Horowitz, Michael
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 non-stimulated, obese non-stimulated and obese-stimulated. Twelve weeks after surgery, glucose uptake and insulin sensitivity were measured using PET during an isoglycemic clamp. Mean whole body insulin sensitivity was lower by 34% (P<0.01) and hepatic glucose uptake rate by 33% (P<0.01) in obese non-stimulated, but was no different in obese-stimulated compared to lean. An improvement in skeletal glucose uptake rate was also observed in obese-stimulated compared to obese non-stimulated groups (P<0.01). Vagal stimulation was associated with increased glucose metabolism in the cingular and prefrontal brain areas. We conclude that chronic vagal stimulation improves insulin sensitivity substantially in diet-induced obesity by both peripheral and central mechanisms.
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