Mesenteric visceral lipectomy using tissue liquefaction technology reverses insulin resistance and causes weight loss in baboons

Abstract

BackgroundVisceral obesity is associated with diabetogenic and atherogenic abnormalities, including insulin resistance and increased risk for cardiometabolic diseases and mortality. Rodent lipectomy studies have demonstrated a causal link between visceral fat and insulin resistance, yet human omentectomy studies have failed to replicate this metabolic benefit, perhaps owing to the inability to target the mesentery. ObjectivesWe aimed to demonstrate that safe and effective removal of mesenteric fat could be achieved in obese insulin-resistant baboons using tissue liquefaction technology. SettingSouthwest National Primate Research Center, San Antonio, Texas. MethodsTissue liquefaction technology has been developed to enable mesenteric visceral lipectomy (MVL) to be safely performed without disturbing the integrity of surrounding nerves and vessels in the mesentary. After an initial MVL optimization study (n = 3), we then performed MVL (n = 4) or sham surgery (n = 2) in a cohort of insulin-resistant baboons, and the metabolic phenotype was assessed via hyperinsulinemic-euglycemic clamps at baseline and 6 weeks later. ResultsMVL led to a 75% improvement in glucose disposal at 6-weeks follow-up (P = .01). Moreover, despite removing only an average of 430 g of mesenteric fat (~1% of total body mass), MVL led to a 14.4% reduction in total weight (P = .001). Thus, these data demonstrate that mesenteric fat can be safely targeted for removal by tissue liquefaction technology in a nonhuman primate, leading to substantial metabolic improvements, including reversal of insulin resistance and weight loss. ConclusionsThese data provide the first demonstration of successful adipose tissue removal from the mesentery in a mammal. Importantly, we have demonstrated that when MVL is performed in obese, insulin-resistant baboons, insulin resistance is reversed, and significant weight loss occurs. Therefore, trials performing MVL in humans with abdominal obesity and related metabolic sequelae should be explored as a potential clinical tool to ameliorate insulin resistance and treat type 2 diabetes.