DISRUPTION OF SYMPATHETIC OUTFLOW TO INTRA-ABDOMINAL ORGANS EMULATES THE METABOLIC EFFECTS OF SLEEVE GASTRECTOMY IN OBESE MICE

Abstract

Although sleeve gastrectomy (SG) is the most commonly performed bariatric surgery in the US, its mechanistic underpinnings have not been fully determined. Thus, we set out to investigate whether SGs effects on the peripheral sympathetic system could mediate the metabolic effects of SG. The celiac-superior mesenteric ganglia (CSMG) lie juxtaposed to the stomach and supply the sympathetic innervation of the stomach, as well as to numerous intra-abdominal organs relevant to metabolism. Here we investigated the effects of SG on the CSMG. SG led to the degeneration of neurons in the CSMG, as evidenced by chromatolysis, which was not found in control mice. Furthermore, CSMG ablation (CGX) completely recapitulated the glycemic and weight loss effects of SG, promoting weight loss at the expense of fat mass in both males and females. Glycemic improvement was robust in males but much more modest in female mice. Norepinephrine tissue content measurement by high performance liquid chromatography revealed that liver, duodenum, and ileum were organs where both SG and CGX displayed evidence of significant sympathetic denervation. Both SG and CGX were associated with increased levels of glucagon-like peptide 1 (GLP-1) and high free fatty acid content in the stools. In conclusion, CSMG neuronal degeneration caused by SG appears to be a mediator of the metabolic effects of this type of bariatric surgery.