Our Program Project is focused on the genetic dissection of metabolic syndrome (MetSyn) in both mouse models and human populations. Our approach is, we believe, unique in its multifaceted and integrative approaches. These include a combination of genetic, genomic, biochemical, physiologic, and bioinformatic analyses. During the current grant cycle, each of the four projects has been highly productive. Project 1 has utilized traditional positional cloning as well as integrative genetics in mice to identify several novel genes affecting adiposity, lipoprotein metabolism, and insulin sensitivity. Project 2 has used linkage and association analysis of human populations to identify a number of novel genes in triglyceride and HDL metabolism. Project 3 has identified and characterized a novel gene controlling the maturation of lipases. Project 4 has carried out detailed molecular studies of the lipin family of proteins, identifying key functions in fat storage and insulin sensitivity. We now propose 4 Projects and 4 Cores. All projects are direct continuations of the present projects, as are the 4 Cores. Project 1 will focus on the integration of mouse and human gene networks for MetSyn and also address the problem of gene-by-environment interactions in MetSyn. Project 2 will further elucidate underlying mechanisms for novel genes identified in human subjects during the present cycle and use both linkage and association in large population samples to further dissect the genetic factors contributing to MetSyn. Project 3 will focus on the biology lipase maturation factor-1, in both mice and humans. Project 4 will examine the role of lipins in adipogenesis and insulin sensitivity and in statin-induced myopathy as well as new genes identified in Project 1. Each of the proposed Projects will interact significantly with each of the other Projects and all of the Cores.
Obesity has increased dramtically in the US and many other parts of the world over recent decades particularly among the young. This will clearly result in an epidemic of MetSyn that is likely to exact a horrific toll. Our Program directly addresses the problem by analysis of the genes and pathways contributing to the clinical complications of MetSyn, therby providing a framework for the development of new therapies.
|Tarling, Elizabeth J; Clifford, Bethan L; Cheng, Joan et al. (2017) RNA-binding protein ZFP36L1 maintains posttranscriptional regulation of bile acid metabolism. J Clin Invest 127:3741-3754|
|Nakano, Haruko; Minami, Itsunari; Braas, Daniel et al. (2017) Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis. Elife 6:|
|Org, Elin; Blum, Yuna; Kasela, Silva et al. (2017) Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort. Genome Biol 18:70|
|Pillai, Indulekha C L; Li, Shen; Romay, Milagros et al. (2017) Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification. Cell Stem Cell 20:218-232.e5|
|von Scheidt, Moritz; Zhao, Yuqi; Kurt, Zeyneb et al. (2017) Applications and Limitations of Mouse Models for Understanding Human Atherosclerosis. Cell Metab 25:248-261|
|Nikkola, Elina; Ko, Arthur; Alvarez, Marcus et al. (2017) Family-specific aggregation of lipid GWAS variants confers the susceptibility to familial hypercholesterolemia in a large Austrian family. Atherosclerosis 264:58-66|
|Schugar, Rebecca C; Shih, Diana M; Warrier, Manya et al. (2017) The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue. Cell Rep 19:2451-2461|
|Rau, Christoph D; Romay, Milagros C; Tuteryan, Mary et al. (2017) Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice. Cell Syst 4:121-128.e4|
|Wang, Huan; Airola, Michael V; Reue, Karen (2017) How lipid droplets ""TAG"" along: Glycerolipid synthetic enzymes and lipid storage. Biochim Biophys Acta 1862:1131-1145|
|Kessler, Thorsten; Wobst, Jana; Wolf, Bernhard et al. (2017) Functional Characterization of the GUCY1A3 Coronary Artery Disease Risk Locus. Circulation 136:476-489|
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