Gastric bypass surgery reduces plasma ceramide subspecies and improves insulin sensitivity in severely obese patients

Abstract

Bariatric surgery is associated with near immediate remission of type 2 diabetes and hyperlipidemia. The mechanisms underlying restoration of normal glucose tolerance postoperatively are poorly understood. Herein, we examined the effect of Roux-en-Y gastric bypass surgery (RYGB) on weight loss, insulin sensitivity, plasma ceramides, proinflammatory markers, and cardiovascular risk factors before and at 3 and 6 months after surgery. Thirteen patients (10 female; age 48.5 ± 2.7 years; BMI, 47.4 ± 1.5 kg/m(2)) were included in the study, all of whom had undergone laparoscopic RYGB surgery. Insulin sensitivity, inflammatory mediators and fasting lipid profiles were measured at baseline, 3 and 6 months postoperatively, using enzymatic analysis. Plasma ceramide subspecies (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC. At 3 months postsurgery, body weight was reduced by 25%, fasting total cholesterol, triglycerides, low-density lipoproteins, and free fatty acids were decreased, and insulin sensitivity was increased compared to presurgery values. These changes were all sustained at 6 months. In addition, total plasma ceramide levels decreased significantly postoperatively (9.3 ± 0.5 nmol/ml at baseline vs. 7.6 ± 0.4 at 3 months, and 7.3 ± 0.3 at 6 months, P < 0.05). At 6 months, the improvement in insulin sensitivity correlated with the change in total ceramide levels (r = -0.68, P = 0.02), and with plasma tumor necrosis factor-α (TNF-α) (r = -0.62, P = 0.04). We conclude that there is a potential role for ceramide lipids as mediators of the proinflammatory state and improved insulin sensitivity after gastric bypass surgery.

Figure 1

Gastric bypass surgery lowers fasting plasma ceramide concentrations. Plasma ceramide concentrations were measured before surgery (grey bars), 3 months (black bars) and 6 months (white bars) post-surgery. Panel (A) illustrates plasma concentration of ceramide subspecies in severely obese patients (N=13) before, 3 months (N=13) and 6 months (N=12) post-RYGB. Panel (B) illustrates total plasma ceramide concentrations at these time points. Data are expressed as means ± S.E.M. * P< 0.05 pre-surgery vs. 3 months and 6 months post surgery.

Figure 2

Correlations between total plasma ceramide and metabolic parameters at 6 months post-surgery. The decrease in total plasma ceramide correlated significantly with (A) excess weight loss (r= −0.61, P=0.04), (B) change in insulin sensitivity (r= −0.68, P=0.02), and (C) change in plasma TNF-α (r=0.64, P=0.03). Percent change was calculated as % change = (Post - Pre)/Post * 100.

Figure 3

Correlations between different plasma ceramide subspecies and metabolic parameters at 6 months post-surgery. For individual ceramide species the decrease in C24:0 correlated significantly with (A) excess weight loss (r= −0.69, p=0.03), and (B) change in insulin sensitivity (r=−0.60, P=0.04), while the decrease in C16:0 ceramide correlated significantly with (C) the decrease in TNF-α (r= 0.72, P=0.02). Percent change was calculated as % change = (Post - Pre)/Post * 100.