Abstract
Background/objectiveChanges in brain metabolism has been investigated thoroughly during unilateral cervical chronic vagal stimulation in epileptic or depressive patients. Bilateral stimulation of the abdominal vagus (aVNS) has received less attention despite the reduction in body weight and an altered feeding behavior in obese animals that could be clinically relevant in obese individuals. Our study aims to examine the changes in brain glucose metabolism (CMRglu) induced by aVNS in obese adult miniature pigs. Dopamine (DAT) and serotonin transporters (SERT) were also quantified to further understand the molecular origins of the alterations in brain metabolism.Subjects/methodsPairs of stimulating electrodes were implanted during laparoscopy on both abdominal vagal trunks in 20 obese adult’s miniature pigs. Half of the animals were permanently stimulated while the remaining were sham stimulated. Two months after the onset of stimulation, dynamic 18FDG PET and 123I-ioflupane SPECT were performed. Food intake, resting energy expenditure and fat deposition were also assessed longitudinally.ResultsFood intake was halved and resting energy expenditure was increased by 60% in aVNS group compared to sham. The gain in body weight was also 38% less in aVNS group compared to sham. Brain metabolic connectivity increased between numerous structures including striatum, mid-brain, amygdala and hippocampus. On the contrary, increased CMRglu were restricted to the thalamus, the periaqueducal grey and the amygdala. DAT binding potential was decreased by about one third in the striatum while SERT was about doubled in the midbrain.ConclusionsOur findings demonstrated that aVNS reduced weight gain as a consequence of diminished daily food intake and increased resting energy expenditure. These changes were associated with enhanced connectivity between several brain areas. A lower striatal DAT together with a doubled mid-brain SERT were likely causative for these changes.
Highlights
Obesity and its consequences are a worldwide public health issue especially because effective reversible bariatric procedures or pharmacological treatments without serious adverse-effects are still in infancy [1]
dopamine transporter (DAT) binding potential was decreased by about one third in the striatum while serotonin transporters (SERT) was about doubled in the midbrain
Our findings demonstrated that chronic bilateral abdominal vagal stimulation (aVNS) reduced weight gain as a consequence of diminished daily food intake and increased resting energy expenditure
Summary
Obesity and its consequences are a worldwide public health issue especially because effective reversible bariatric procedures or pharmacological treatments without serious adverse-effects are still in infancy [1]. Central neuromodulation using vagal stimulation might become an alternate therapeutic tool [2] since it increased satiation [3], reduced food intake [2] and increased energy expenditure [4] without adverse side effects [5] It restored insulin sensitivity in obese animals and improved the insulin-dependent glucose metabolism of several organs including the brain [6]. The maximum effectiveness towards weight loss was observed with bilateral stimulation performed at the level of the abdominal branches (aVNS) [7] It is significantly more complicated than the one used for refractory epilepsy or depression which involve stimulation of the left cervical vagus only [8]. Since it was performed below the cardiac branches, it avoids unwanted cardiac side effects [5]
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