Please use this identifier to cite or link to this item: https://doi.org/10.3389/fphys.2019.00379
Title: Plasma Protein and MicroRNA Biomarkers of Insulin Resistance: A Network-Based Integrative -Omics Analysis
Authors: Choi, Hyungwon 
Koh, Hiromi WL
Zhou, Lihan 
Cheng, He 
Loh, Tze Ping 
Rizi, Ehsan Parvaresh
Toh, Sue Anne
Ronnett, Gabriele
Huang, Bevan E
Khoo, Chin Meng 
Keywords: Science & Technology
Life Sciences & Biomedicine
Physiology
obesity
insulin resistance
proteomics
microRNAs
network analysis
ADIPOSE-TISSUE
OBESITY
PATHOGENESIS
INFLAMMATION
MUSCLE
LIVER
Issue Date: 5-Apr-2019
Publisher: FRONTIERS MEDIA SA
Citation: Choi, Hyungwon, Koh, Hiromi WL, Zhou, Lihan, Cheng, He, Loh, Tze Ping, Rizi, Ehsan Parvaresh, Toh, Sue Anne, Ronnett, Gabriele, Huang, Bevan E, Khoo, Chin Meng (2019-04-05). Plasma Protein and MicroRNA Biomarkers of Insulin Resistance: A Network-Based Integrative -Omics Analysis. FRONTIERS IN PHYSIOLOGY 10. ScholarBank@NUS Repository. https://doi.org/10.3389/fphys.2019.00379
Abstract: Although insulin resistance (IR) is a key pathophysiologic condition underlying various metabolic disorders, impaired cellular glucose uptake is one of many manifestations of metabolic derangements in the human body. To study the systems-wide molecular changes associated with obesity-dependent IR, we integrated information on plasma proteins and microRNAs in eight obese insulin-resistant (OIR, HOMA-IR > 2.5) and nine lean insulin-sensitive (LIS, HOMA-IR < 1.0) normoglycemic males. Of 374 circulating miRNAs we profiled, 65 species increased and 73 species decreased in the OIR compared to the LIS subjects, suggesting that the overall balance of the miRNA secretome is shifted in the OIR subjects. We also observed that 40 plasma proteins increased and 4 plasma proteins decreased in the OIR subjects compared to the LIS subjects, and most proteins are involved in metabolic and endocytic functions. We used an integrative -omics analysis framework called iOmicsPASS to link differentially regulated miRNAs with their target genes on the TargetScan map and the human protein interactome. Combined with tissue of origin information, the integrative analysis allowed us to nominate obesity-dependent and obesity-independent protein markers, along with potential sites of post-transcriptional regulation by some of the miRNAs. We also observed the changes in each -omics platform that are not linked by the TargetScan map, suggesting that proteins and microRNAs provide orthogonal information for the progression of OIR. In summary, our integrative analysis provides a network of elevated plasma markers of OIR and a global shift of microRNA secretome composition in the blood plasma.
Source Title: FRONTIERS IN PHYSIOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/155332
ISSN: 1664042X
DOI: 10.3389/fphys.2019.00379
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