Lipidomic profiling before and after Roux-en-Y gastric bypass in obese patients with diabetes

Abstract

Bariatric surgery is a well-established approach to improve metabolic disease in morbidly obese patients with high cardiovascular risk. The post-operative normalization of lipid metabolism has a central role in the prevention of future cardiovascular events. The aim of the present study therefore was to characterize changes of plasma lipidomic patterns, consisting of 229 lipid species of 13 lipid classes, 3 months after Roux-en-Y gastric bypass (RYGB) in morbidly obese patients with and without diabetes. RYGB resulted in a 15-32% decrease of body mass index, which was associated with a significant reduction of total cholesterol (TC, -28.3%; P=0.02), LDL-cholesterol (LDL-C, -26.8%; P=0.03) and triglycerides (TGs, -63.0%; P=0.05) measured by routine clinical chemistry. HDL-cholesterol remained unchanged. The effect of RYGB on the plasma lipidomic profile was characterized by significant decreases of 87 lipid species from triacylglycerides (TAGs), cholesterol esters (CholEs), lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), phosphatidylethanolamine ethers (PEOs), phosphatidylinositols (PIs) and ceramides (Cers). The total of plasma lipid components exhibited a substantial decline of 32.6% and 66 lipid species showed a decrease by over 50%. A direct correlation with HbA1C values could be demonstrated for 24 individual lipid species (10 TAG, three CholE, two LPC, one lysophosphatidylcholine ethers (LPCO) (LPC ether), one PC, two phosphatidylcholine ethers (PCO) and five Cer). Notably, two lipid species (TAG 58:5 and PEO 40:5) were inversely correlated with HbA1C. LPCO, as single whole lipid class, was directly related to HbA1C. These data indicate that RYGB-induced modulation of lipidomic profiles provides important information about post-operative metabolic adaptations and might substantially contribute to improvements of glycemic control. These striking changes in the human plasma lipidome may explain acute, weight independent and long-term effects of RYGB on the cardiovascular system, mental status and immune regulation.

Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk

“…We observed many significant associations between PC-and SM-related factors with variables of the blood lipid profile. Graessen et al (12) showed a decrease in many PC species with improvement of the blood lipid profile in patients who had undergone Roux-en-Y gastric bypass surgery. In our study, we found that levels of PCaa, the most abundant phosphatidylcholine subtype, correlated with plasma cholesterol and triglyceride levels.…”

“…Sphingolipids, particularly sphingomyelins (SM), are ceramide precursors and usually colocalize with cholesterol on cell membranes and LDL surface (21). Evidence suggests that ceramide concentrations are associated with insulin resistance (12,21,46). The ratio of kynurenine to tryptophan levels (Kyn/Trp), an increasingly recognized marker of inflammation and metabolic alterations, has been shown to be high in adult overweight or obese individuals (24,53), and also appears to be related to waist circumference independent of age (24).…”

Form(ul)ation of adipocytes by lipids

“…[15][16][17][18]21 Lipidomics of blood samples has been also performed following regimens of weight loss by diet, exercise, bariatric surgery or drug therapy. 19,22,23 The results demonstrate that weight loss produces a characteristic lipid signature that is in part opposite to the characteristic lipid signature of patients with diabetes. The plasma signature of weight loss is characterized by TG with longer and desaturated acyl chains, 19,22 and by a decrease in total plasma levels of TG, CE and ceramides.…”

“…The plasma signature of weight loss is characterized by TG with longer and desaturated acyl chains, 19,22 and by a decrease in total plasma levels of TG, CE and ceramides. 22,23 In summary, lipidomics is a useful diagnostic tool to discover bio-markers associated with metabolic syndrome with its various manifestations, relying on global changes in systemic lipid metabolism. To understand the biologic significance that underlies these lipid signatures, lipidomics may be used as a new scientific avenue to decipher lipid profiles of tissues, including adipocytes, in humans and animal models.…”

Serum fatty acid profiling within distinct lipid fractions provides a more robust indicator of insulin resistance in humans than total triglyceride and fatty acid profiles

“…This is relevant because T2D patients commonly have elevated circulating levels of VLDL--c and reduced HDL--c compared to non--T2D individuals [126,127]; suggesting that hepatic PC synthesis and secretion levels may be associated with T2D risk. Aside from the recent evidence presented by Graessler et al, which suggested that small reductions in fasting glucose levels are associated with reductions in total PC levels [128], few investigations have reported on differences in total blood PC concentrations between healthy and T2D individuals. As such, future investigations may find it interesting to investigate the PC fraction more closely in order to better understand the associations between hepatic lipoprotein synthesis, serum PC, and IR.…”