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

https://doi.org/10.1016/j.soard.2018.03.004Get rights and content

Abstract

Background

Visceral 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.

Objectives

We aimed to demonstrate that safe and effective removal of mesenteric fat could be achieved in obese insulin-resistant baboons using tissue liquefaction technology.

Setting

Southwest National Primate Research Center, San Antonio, Texas.

Methods

Tissue 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.

Results

MVL 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.

Conclusions

These 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.

Section snippets

Animals

For optimization studies performed in Phase I, a total of 3 male baboons with obesity (weight>37 kg, %fat>21) were carefully selected [28]. For the Phase II efficacy study, a total of 9 nondiabetic obese animals (mean age = 12.0 ± 1.2 yr; mean glycated hemoglobin [HbA1C] 4.8 ± .4%) with the highest HbA1C levels (Table 1) were then enrolled into the study from the colony housed at the Southwest National Primate Research Center, Texas Biomedical Research Institute (San Antonio, TX). Baseline

Optimization

For Phase I, we performed an initial safety trial in obese male baboons (n = 3). For each procedure, approximately 125 to 150 g of MF was surgically removed using TLT (Fig. 1A). In all surgeries, the majority of the operating time was spent starting and stopping the fat removal activity in an effort to determine the optimal parameters and settings for removing VF using the TLT system. As these studies were intended for optimization, the effect on MF removal efficiency was tested with numerous

Discussion

Here, we have demonstrated that safe and effective removal of MF can be achieved in obese insulin-resistant baboons using TLT. We were able to remove up to 75% to 80% of all visible adipose tissue in the mesentery without complications, which we estimate to be approximately 40% of total VF stores, based upon prior estimates of abdominal fat mass in baboons [36]. To our knowledge, this is the first report of significant adipose tissue removal from the mesentery in any mammalian species.

Conclusion

We have demonstrated here that significant quantities of mesenteric visceral fat can be safely and effectively surgically excised, using TLT, in adult male baboons, thereby providing the first important proof-of-concept that such a surgical intervention may be feasible in humans. Importantly, this procedure produced marked metabolic benefits in previously insulin-resistant, male, obese baboons, reversing insulin resistance and promoting significant weight loss. This suggests that meaningful

Disclosures

The authors have no commercial associations that might be a conflict of interest in relation to this article.

Mark Andrew, MD is the Founder and Chief Scientific Officer of Andrew Technologies, and he does have a financial interest in Andrew Technologies.

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  • Cited by (0)

    M. S. A. and D. M. H equally contributed to this work.

    Supported by National Institutes of Health Grant R43 DK112428.

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