Lipidomic profiling reveals early-stage metabolic dysfunction in overweight or obese humans

被引:32
|
作者
Mousa, Aya [1 ]
Naderpoor, Negar [1 ]
Mellett, Natalie [2 ]
Wilson, Kirsty [3 ]
Plebanski, Magdalena [3 ,4 ]
Meikle, Peter J. [2 ]
de Courten, Barbora [1 ]
机构
[1] Monash Univ, MCHRI, Sch Publ Hlth & Prevent Med, 43-51 Kanooka Grove, Clayton, Vic 3168, Australia
[2] Baker Heart & Diabet Inst, Metabol Lab, 75 Commercial Rd, Melbourne, Vic 3004, Australia
[3] Monash Univ, Dept Immunol & Pathol, 89 Commercial Rd, Melbourne, Vic 3004, Australia
[4] RMIT Univ, Sch Hlth & Biomed Sci, Corner Janefield Dr & Plenty Rd, Bundoora, Vic 3083, Australia
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 2019年 / 1864卷 / 03期
基金
澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;
关键词
Lipid metabolism; Lipidomics; Diabetes; Insulin secretion; Metabolic dysfunction; Obesity; SKELETAL-MUSCLE; INSULIN-RESISTANCE; PLASMA CERAMIDES; POTENTIAL ROLE; LYSOPHOSPHATIDYLINOSITOL; ACID; PHOSPHATIDYLETHANOLAMINE; MITOCHONDRIA; HOMEOSTASIS; DEFICIENCY;
D O I
10.1016/j.bbalip.2018.12.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Advances in mass spectrometry and lipidomics techniques are providing new insights into the role of lipid metabolism in obesity-related diseases. However, human lipidomic studies have been inconsistent, owing to the use of indirect proxy measures of metabolic outcomes and relatively limited coverage of the lipidome. Here, we employed comprehensive lipid profiling and gold-standard metabolic measures to test the hypothesis that distinct lipid signatures in obesity may signify early stages of pathogenesis toward type 2 diabetes. Methods: Using high-performance liquid chromatography-electrospray tandem mass spectrometry, we profiled > 450 lipid species across 26 classes in 65 overweight or obese non-diabetic individuals. Intensive metabolic testing was conducted using direct gold-standard measures of adiposity (% body fat by dual X-ray absorptiometry), insulin sensitivity (hyperinsulinaemic-euglycaemic clamps), and insulin secretion (intravenous glucose tolerance tests), as well as measurement of serum inflammatory cytokines and adipokines (multiplex assays; flow cytometry). Univariable and multivariable linear regression models were computed using Matlab R2011a, and all analyses were corrected for multiple testing using the Benjamini-Hochberg method. Results: We present new evidence showing a strong and independent positive correlation between the lysophosphatidylinositol (LPI) lipid class and insulin secretion in vivo in humans (beta [95% CI] = 781.9 [353.3, 1210.4], p = 0.01), supporting the insulinotropic effects of LPI demonstrated in mouse islets. Dihydroceramide, a sphingolipid precursor, was independently and negatively correlated with insulin sensitivity (13 [95% CI] = -1.9 [ - 2.9, - 0.9], p = 0.01), indicating a possible upregulation in sphingolipid synthesis in obese individuals. These associations remained significant in multivariable models adjusted for age, sex, and % body fat. The dihexosylceramide class correlated positively with interleukin-10 before and after adjustment for age, sex, and % body fat (p = 0.02), while the phosphatidylethanolamine class and its vinyl ether-linked (plasmalogen) derivatives correlated negatively with % body fat in both univariable and age- and sex-adjusted models (all p < 0.04). Conclusions: Our data suggest that these lipid classes may signify early pathogenesis toward type 2 diabetes and could serve as novel therapeutic targets or biomarkers for diabetes prevention.
引用
收藏
页码:335 / 343
页数:9
相关论文
共 50 条
  • [31] Metabolic profiling reveals growth stage variability in diatom exudates
    Barofsky, Alexandra
    Vidoudez, Charles
    Pohnert, Georg
    LIMNOLOGY AND OCEANOGRAPHY-METHODS, 2009, 7 : 382 - 390
  • [32] METABOLIC COMPONENTS AND RECURRENCE IN EARLY-STAGE CERVICAL CANCER
    Hwang, I. C.
    DIABETES RESEARCH AND CLINICAL PRACTICE, 2014, 106 : S177 - S177
  • [33] Robotic surgery in obese patients with early-stage endometrial cancer
    Zhao, Yanyan
    Liu, Zhongyu
    Yu, Ling
    Liu, Sai
    Yan, Hong
    Zhang, Yan
    Yao, Yuanqing
    VIDEOSURGERY AND OTHER MINIINVASIVE TECHNIQUES, 2020, 15 (01) : 171 - 175
  • [34] Metabolic components and recurrence in early-stage cervical cancer
    Ahn, Hee Kyung
    Shin, Jin Woo
    Ahn, Hong Yup
    Park, Chan-Yong
    Lee, Nak Woo
    Lee, Jae Kwan
    Hwang, In Cheol
    TUMOR BIOLOGY, 2015, 36 (03) : 2201 - 2207
  • [35] Serum Protein Profiling Reveals a Landscape of Inflammation and Immune Signaling in Early-stage COVID-19 Infection
    Hou, Xin
    Zhang, Xiaomei
    Wu, Xian
    Lu, Minya
    Wang, Dan
    Xu, Meng
    Wang, Hongye
    Liang, Te
    Dai, Jiayu
    Duan, Hu
    Xu, Yingchun
    Yu, Xiaobo
    Li, Yongzhe
    MOLECULAR & CELLULAR PROTEOMICS, 2020, 19 (11) : 1749 - 1759
  • [36] A serum lipidomic strategy revealed potential lipid biomarkers for early-stage cervical cancer
    Cheng, Feng
    Wen, Zhifa
    Feng, Xiaodan
    Wang, Xiaoman
    Chen, Yajun
    LIFE SCIENCES, 2020, 260
  • [37] Metabolic profiling of adipose tissues in metabolic dysfunction-associated steatohepatitis (MASH): insights from lipidomic, proteomic, and epigenetic analyses in morbidly obese patients undergoing bariatric surgery
    Placed-Gallego, Cristina
    Manuel Jimenez-Aguilar, Juan
    Onoiu, Alina-Iuliana
    Cambra-Cortes, Vicente
    Jimenez-Franco, Andrea
    Martinez-Navidad, Cristian
    Castane, Helena
    Camps, Jordi
    Joven, Jorge
    JOURNAL OF HEPATOLOGY, 2024, 80 : S583 - S584
  • [38] Comprehensive Lipidome Profiling of the Kidney in Early-Stage Diabetic Nephropathy
    Hou, Biyu
    He, Ping
    Ma, Peng
    Yang, Xinyu
    Xu, Chunyang
    Lam, Sin Man
    Shui, Guanghou
    Yang, Xiuying
    Zhang, Li
    Qiang, Guifen
    Du, Guanhua
    FRONTIERS IN ENDOCRINOLOGY, 2020, 11
  • [39] Proteomic profiling for detection of early-stage heart failure in the community
    Cauwenberghs, Nicholas
    Sabovcik, Frantisek
    Magnus, Alessio
    Haddad, Francois
    Kuznetsova, Tatiana
    ESC HEART FAILURE, 2021, 8 (04): : 2928 - 2939
  • [40] Proteomic profiling for detection of early-stage heart failure in the community
    Cauwenberghs, N.
    Sabovcik, F.
    Haddad, F.
    Kuznetsova, T.
    EUROPEAN HEART JOURNAL, 2021, 42 : 861 - 861