Triglycerides analysis in adipose tissue from insulin sensitive and insulin resistance obese patients

Abstract

IntroductionObesity triggers changes in adipose tissue composition and functionality that contribute to the progression of obesity‐associated metabolic diseases such as insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain insulin sensitivity and show better adipose tissue functions compared to their equally obese insulin resistance counterparts. Lipid intermediates produced during triaclyglycerols (TAG) synthesis and lipolysis interfere with the intracellular insulin signaling pathway and development of insulin resistance. This study aims to compare TAG species and their fatty acid composition in adipose tissues from insulin sensitive (IS) and insulin resistant (IR) individuals.MethodsHuman subcutaneous and Omental adipose tissue biopsies were obtained from 64 clinically characterized obese individuals during weight reduction surgery. TAG were extracted from the adipose tissues using the Bligh& Dyer method then subjected to non‐aqueous revers phase UHPLC and full scan mass spectrometry acquisition and data dependent MS/MS on the Thermo LTQ dual cell linear ion trap. TAG and their fatty acid contents were compared between IS and IR individuals and their levels were correlated with metabolic traits of participants and the adipogenesis potential of preadipocyte cultures established from their adipose tissues.ResultsData revealed over 120 unique TAG species identified based on their exact mass in adipose tissues. Analysis of TAG levels suggested a number of depot‐specific TAG species irrespective of insulin sensitivity status as well as specific TAG that decreased or increased with disease progression. Significant correlations between TAG species and metabolic traits were observed including age, body mass index, total cholesterol, interleukin‐6, C‐reactive protein, alkaline phosphatase and adipogenic potential.ConclusionPilot data suggest that adipose tissues from obese individuals exhibit depot and insulin response‐specific lipid signatures that may contribute to the increased risk of IR and T2DM. Future experiments will investigate the functional relevance of these specific lipidomic profiles.Support or Funding InformationAnti‐Doping Lab Qatar Result 2 General characteristics of participants Variables IS (N=18) IR (N=35) T2DM (N=11) p value Age (year) 30.9 (8.5) 32.1 (8.7) 42.7 (11.0) 0.002 BMI (kg.m−2) 41.6 (7.6) 42.4 (6.8) 44 (8.1) 0.71 SBP (mmHg) 122 (17.6) 35 (127.08) 132 (5.4) 0.27 DBP (mmHg) 71.9 (12.5) 35 (72.2) 79.2 (6.2) 0.25 MAP 86.4 (8.2) 90.4 (13.6) 97.4 (6.1) 0.06 Cholesterol (mmol/L) 4.4 (0.81) 4.6 (0.69) 4.8 (0.64) 0.25 LDL (mmol/L) 2.6 (0.72) 2.92 (0.71) 2.6 (0.69) 0.33 HDLC (mmol/L) 1.3 (0.3) 1.19 (0.28) 1.15 (0.26) 0.16 Triglyceride (mmol/L) 1.14 (0.74) 1.29 (0.59) 2.35 (1.16) 0.00 Leptin (ng/ml) 68.07 (30.5) 62.09 (25.1) 39.8 (31.5) 0.04 Adiponectin (ng/ml) 5.6 (4.9) 3.7 (2.2) 3.05(1.09) 0.12 IL‐6 (pg/ml) 3.8 (2.04) 4.3 (2.4) 4.4 (2.3) 0.70 FBG (mmol/L) 4.9 (0.7) 5.8 (1.06) 9.5 (5.8) 0.00 Insulin (mIU/L) 7.07 (2.2) 18.3 (9.05) 16.6 (7.1) 0.00 HOMA‐IR 1.4 (0.4) 5.2 (3.2) 6.6(3.9) 0.00 Compared to BMI‐matched IS subjects, IR and T2DM individuals had higher circulating levels of TAG and lower leptin