Abstract：
:Elevated plasma cholesterol and type 2 diabetes (T2D) are associated with coronary artery disease (CAD). Individuals treated with cholesterol-lowering statins have increased T2D risk, while individuals with hypercholesterolemia have reduced T2D risk. We explore the relationship between lipid and glucose control by constructing network models from the STARNET study with sequencing data from seven cardiometabolic tissues obtained from CAD patients during coronary artery by-pass grafting surgery. By integrating gene expression, genotype, metabolomic, and clinical data, we identify a glucose and lipid determining (GLD) regulatory network showing inverse relationships with lipid and glucose traits. Master regulators of the GLD network also impact lipid and glucose levels in inverse directions. Experimental inhibition of one of the GLD network master regulators, lanosterol synthase (LSS), in mice confirms the inverse relationships to glucose and lipid levels as predicted by our model and provides mechanistic insights.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Cohain AT,Barrington WT,Jordan DM,Beckmann ND,Argmann CA,Houten SM,Charney AW,Ermel R,Sukhavasi K,Franzen O,Koplev S,Whatling C,Belbin GM,Yang J,Hao K,Kenny EE,Tu Z,Zhu J,Gan LM,Do R,Giannarelli C,Kovacic JC,Rdoi
10.1038/s41467-020-20750-8subject
Has Abstractpub_date
2021-01-22 00:00:00pages
547issue
1issn
2041-1723pii
10.1038/s41467-020-20750-8journal_volume
12pub_type
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