Lipidomics Reveals Associations of Phospholipids With Obesity and Insulin Resistance in Young Adults

• Published in: The journal of clinical endocrinology and metabolism Vol. 101; no. 3; pp. 871 - 879
• Main Authors: Rauschert, Sebastian, Uhl, Olaf, Koletzko, Berthold, Kirchberg, Franca, Mori, Trevor A., Huang, Rae-Chi, Beilin, Lawrence J., Hellmuth, Christian, Oddy, Wendy H.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.03.2016; Copyright by The Endocrine Society
• Subjects: Adult; Biomarkers; Body mass index; Cholesterol; Cohort Studies; Diabetes mellitus; Female; High density lipoprotein; Homeostasis; Humans; Insulin Resistance; Lysophosphatidylcholine; Male; Mass spectroscopy; Metabolomics; Obesity; Obesity - blood; Obesity - etiology; Phospholipids; Phospholipids - blood; Population studies; Public health; Sphingomyelins - blood; Weight; Young Adult; Young adults
• Online Access: Get full text
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2015-3525

Context:Obesity and related diseases have become a global public health burden. Identifying biomarkers will lead to a better understanding of the underlying mechanisms associated with obesity and the pathways leading to insulin resistance (IR) and diabetes.Objective:This study aimed to identify the lipidomic biomarkers associated with obesity and IR using plasma samples from a population-based cohort of young adults.Design and Setting:The Western Australian Pregnancy Cohort (Raine) study enrolled 2900 pregnant women from 1989 to 1991. The 20-year follow-up was conducted between March 2010 and April 2012.Participants and Samples:Plasma samples from 1176 subjects aged 20 years were analyzed using mass spectrometry-based metabolomics.Main Outcome Measures:Associations of analytes with markers of obesity and IR including body mass index, waist circumference, homeostasis model assessment (HOMA-IR), and insulin were examined. Analyses were stratified by body mass index and adjusted for lifestyle and other factors.Results:Waist circumference was positively associated with seven sphingomyelins and five diacylphosphatidylcholines and negatively associated with two lysophosphatidylcholines. HOMA-IR was negatively associated with two diacylphosphatidylcholines and positively with one lysophosphatidylcholine and one diacylphosphatidylcholine. No significant association was found in the obese/overweight group of the HOMA-IR model. In the normal-weight group, one lysophosphatidylcholine was increased.Conclusion:A possible discriminative effect of sphingomyelins, particularly those with two double bonds, and lysophosphatidylcholines was identified between subjects with normal weight and obesity independent of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol concentrations. Our results suggest weight status-dependent mechanisms for the development of IR with lysophosphatidylcholine C14:0 as a key metabolite in nonobese IR.