Greater omentectomy improves insulin sensitivity in nonobese dogs

Abstract

Visceral adiposity is strongly associated with insulin resistance; however, little evidence directly demonstrates that visceral fat per se impairs insulin action. Here, we examine the effects of the surgical removal of the greater omentum and its occupying visceral fat, an omentectomy (OM), on insulin sensitivity (S(I)) and beta-cell function in nonobese dogs. Thirteen male mongrel dogs were used in this research study; animals were randomly assigned to surgical treatment with either OM (n = 7), or sham-surgery (SHAM) (n = 6). OM failed to generate measurable changes in body weight (+2%; P = 0.1), or subcutaneous adiposity (+3%; P = 0.83) as assessed by magnetic resonance imaging (MRI). The removal of the greater omentum did not significantly reduce total visceral adipose volume (-7.3 +/- 6.4%; P = 0.29); although primary analysis showed a trend for OM to increase S(I) when compared to sham operated animals (P = 0.078), further statistical analysis revealed that this minor reduction in visceral fat alleviated insulin resistance by augmenting S(I) of the periphery (+67.7 +/- 35.2%; P = 0.03), as determined by the euglycemic-hyperinsulinemic clamp. Insulin secretory response during the hyperglycemic step clamp was not directly influenced by omental fat removal (presurgery 6.82 +/- 1.4 vs. postsurgery: 6.7 +/- 1.2 pmol/l/mg/dl, P = 0.9). These findings provide new evidence for the deleterious role of visceral fat in insulin resistance, and suggest that a greater OM procedure may effectively improve insulin sensitivity.

FIGURE 1. Effect of surgical treatment on adiposity

(A): Abdominal MRI images of representative dogs from OM and SHAM treatment groups. Fat tissue appears yellow while all other tissue appears red. Visceral fat is located within the peritoneal cavity, while subcutaneous fat is outside of the peritoneum. (B): Relative changes in visceral and subcutaneous adiposity in OM and SHAM-treated dogs. (C) Axial MRI images of excised omentum from OM-treated dogs.

FIGURE 2. Effect of surgical treatment on insulin sensitivity

(A) Insulin sensitivity (×10⁴ dl·kg^-1·min^-1·pM^-1) by individual dogs and means ± SE pre- and post-omentectomy (left panel) and sham (right panel) surgery. (B) Linear regression depicting the relationship between change in the visceral adipose volume vs. the change in insulin sensitivity with omentectomy and sham-surgery. *P≤0.05 compared to pre-surgery by paired t-tests.

FIGURE 3. Euglycemic- hyperinsulinemic clamp parameters

Time-course data of glucose uptake (A), glucose production (B), plasma insulin (C), and plasma FFA (D) pre- and post-omentectomy and sham-surgery, respectively. Pre-surgery: closed symbols. Post-surgery: open symbols. *P≤0.05 compared to pre-surgery by paired t-tests.

FIGURE 4. Pancreatic β-cell function

Pre- and post- omentectomy (A) and sham (B) surgery. The disposition index with omentectomy (C) and sham-treatment (D). Pre-surgery: closed symbols and solid lines; post-surgery: open symbols and dashed lines.