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A Lipid Signature with Perturbed Triacylglycerol Co-Regulation, Identified from Targeted Lipidomics, Predicts Risk for Type 2 Diabetes and Mediates the Risk from Adiposity in Two Prospective Cohorts of Chinese Adults
Clinical Chemistry ( IF 7.1 ) Pub Date : 2022-06-16 , DOI: 10.1093/clinchem/hvac090 Gaokun Qiu 1 , Hao Wang 1 , Qi Yan 1 , Hongxia Ma 2 , Rundong Niu 1 , Yanshou Lei 1 , Yang Xiao 1 , Lue Zhou 1 , Handong Yang 3 , Chengwei Xu 3 , Xiaomin Zhang 1 , Meian He 1 , Huiru Tang 4, 5 , Zhibin Hu 2 , An Pan 1 , Hongbing Shen 2 , Tangchun Wu 1
Clinical Chemistry ( IF 7.1 ) Pub Date : 2022-06-16 , DOI: 10.1093/clinchem/hvac090 Gaokun Qiu 1 , Hao Wang 1 , Qi Yan 1 , Hongxia Ma 2 , Rundong Niu 1 , Yanshou Lei 1 , Yang Xiao 1 , Lue Zhou 1 , Handong Yang 3 , Chengwei Xu 3 , Xiaomin Zhang 1 , Meian He 1 , Huiru Tang 4, 5 , Zhibin Hu 2 , An Pan 1 , Hongbing Shen 2 , Tangchun Wu 1
Affiliation
Background The roles of individual and co-regulated lipid molecular species in the development of type 2 diabetes (T2D) and mediation from metabolic risk factors remain unknown. Methods We conducted profiling of 166 plasma lipid species in 2 nested case-control studies within 2 independent cohorts of Chinese adults, the Dongfeng-Tongji and the Jiangsu non-communicable disease cohorts. After 4.61 (0.15) and 7.57 (1.13) years’ follow-up, 1039 and 520 eligible participants developed T2D in these 2 cohorts, respectively, and controls were 1:1 matched to cases by age and sex. Results We found 27 lipid species, including 10 novel ones, consistently associated with T2D risk in the 2 cohorts. Differential correlation network analysis revealed significant correlations of triacylglycerol (TAG) 50:3, containing at least one oleyl chain, with 6 TAGs, at least 3 of which contain the palmitoyl chain, all downregulated within cases relative to controls among the 27 lipids in both cohorts, while the networks also both identified the oleyl chain-containing TAG 50:3 as the central hub. We further found that 13 of the 27 lipids consistently mediated the association between adiposity indicators (body mass index, waist circumference, and waist-to-height ratio) and diabetes risk in both cohorts (all P < 0.05; proportion mediated: 20.00%, 17.70%, and 17.71%, and 32.50%, 28.73%, and 33.86%, respectively). Conclusions Our findings suggested notable perturbed co-regulation, inferred from differential correlation networks, between oleyl chain- and palmitoyl chain-containing TAGs before diabetes onset, with the oleyl chain-containing TAG 50:3 at the center, and provided novel etiological insight regarding lipid dysregulation in the progression from adiposity to overt T2D.
更新日期：2022-06-16
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