A5020562578- Peroxisome Proliferator-Activated Receptors
- Gut microbiota and health
- Liver Disease Diagnosis and Treatment
- Adipose Tissue and Metabolism
- Genetic Associations and Epidemiology
- Diet and metabolism studies
- Genetic Mapping and Diversity in Plants and Animals
- Atherosclerosis and Cardiovascular Diseases
- Cholesterol and Lipid Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Lipid metabolism and disorders
- Dietary Effects on Health
- Lipoproteins and Cardiovascular Health
- Fatty Acid Research and Health
- Nutrition, Genetics, and Disease
- Pancreatic function and diabetes
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Tryptophan and brain disorders
- Cancer, Lipids, and Metabolism
- Alcohol Consumption and Health Effects
- Lipid metabolism and biosynthesis
- Diet, Metabolism, and Disease
- Metabolomics and Mass Spectrometry Studies
- Gout, Hyperuricemia, Uric Acid
- Epigenetics and DNA Methylation
University of California, Los Angeles
2013-2023
UCLA Health
2008-2018
Western University
2011
Cedars-Sinai Medical Center
2011
Broad Institute
2011
Hamilton Health Sciences
2011
McMaster University
2011
Center for Human Genetics
2011
Harvard University
2008-2011
Population Health Research Institute
2011
Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes in turn induce changes higher-order disease traits. Therefore, identifying the vary response DNA and also associate traits has potential provide functional information required only identify validate susceptibility genes affected by DNA, understand networks which such operate how these Toward end, we profiled more than 39,000 transcripts...
We previously reported quantitation of gut microbiota in a panel 89 different inbred strains mice, and we now examine the question sex differences composition. When total population 689 mice was examined together, several taxa exhibited significant abundance between sexes but larger number were observed at single strain level, suggesting that can be obscured by host genetics environmental factors. also subset on chow high fat diets sex-by-diet interactions. further investigated using...
Leukotrienes are inflammatory mediators generated from arachidonic acid (polyunsaturated n–6 fatty acid) by the enzyme 5-lipoxygenase. Since atherosclerosis involves arterial inflammation, we hypothesized that a polymorphism in 5-lipoxygenase gene promoter could relate to humans and this effect interact with dietary intake of competing substrates.
We previously reported the identification of a locus on mouse chromosome 6 that confers almost total resistance to atherogenesis, even hypercholesterolemic (LDL receptor-null) background. 5-Lipoxygenase (5-LO) is rate-limiting enzyme in leukotriene synthesis and was among candidate genes we examined. The levels 5-LO mRNA were reduced about 5-fold congenic strain, designated CON6, containing resistant region derived from CAST/Ei strain (CAST), as compared with background C57BL/6J (B6) strain....
Genetics provides a potentially powerful approach to dissect host-gut microbiota interactions. Toward this end, we profiled gut using 16s rRNA gene sequencing in panel of 110 diverse inbred strains mice. This has previously been studied for wide range metabolic traits and can be used high-resolution association mapping. Using SNP-based with linear mixed model, estimated the heritability composition. We conclude that, controlled environment, genetic background accounts substantial fraction...
The gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome Men (METSIM) study. We investigate relationships with variety of factors have an impact on development metabolic cardiovascular traits. identify novel associations between fasting serum levels number metabolites, including fatty acids, amino lipids,...
The microbes and microbial pathways that influence host inflammatory disease progression remain largely undefined. Here, we show variation in atherosclerosis burden is partially driven by gut microbiota associated with circulating levels of uric acid (UA) mice humans. We identify bacterial taxa spanning multiple phyla, including Bacillota, Fusobacteriota, Pseudomonadota, use purines, UA as carbon energy sources anaerobically. a gene cluster encodes key steps anaerobic purine degradation...
Abstract —Some observations have suggested that the extracellular group IIa phospholipase A 2 (sPLA ), previously implicated in chronic inflammatory conditions such as arthritis, may contribute to atherosclerosis. We examined this hypothesis by studying transgenic mice expressing human enzyme. Compared with nontransgenic littermates, exhibited dramatically increased atherosclerotic lesions when maintained on a high-fat, high-cholesterol diet. Surprisingly, also significant low-fat chow...
Minimally modified low density lipoprotein (MM-LDL), derived by mild iron oxidation or prolonged storage at 4 degrees C, has been shown to induce certain inflammatory responses in vascular cells tissue culture. These include induction of monocyte (but not neutrophil) adherence endothelial (EC), EC production colony stimulating factors (CSF), and smooth muscle cell chemotactic protein (MCP-1). To test for biologic activity vivo, microgram quantities MM-LDL were injected into mice, sera...
Obesity has repeatedly been linked to reorganization of the gut microbiome, yet this point obesity therapeutics have targeted exclusively toward human host. Here, we show that microbe-targeted inhibition trimethylamine N-oxide (TMAO) pathway protects mice against metabolic disturbances associated with diet-induced (DIO) or leptin deficiency (
We analyzed the inheritance of body fat, leptin levels, plasma lipoprotein insulin and related traits in an intercross between inbred mouse strains CAST/Ei C57BL/6J. mice are unusually lean, with only approximately 8% weight as whereas C57BL/6J have 18% fat. Quantitative trait locus analysis using > 200 F2 revealed highly significant loci (lod scores 4.3) on chromosomes 2 (three separate loci) 9 that contribute to fat-pad mass for a high-fat diet. Some also influenced levels either chow or...
Previous studies have shown that distal mouse chromosome 1 contains the apolipoprotein AII (apoAII) gene, encoding second most abundant in high density lipoproteins (HDLs), as well a gene termed Ath-1 controls aortic fatty streak development and HDL cholesterol levels response to high-fat, high-cholesterol diet. We report genetic confirming genes are distinct. Using molecular markers for 1, we further mapped two genes, our results indicate they separated by minimum of 2 cM. also evidence...
Rare variant accumulation studies can implicate genes in disease susceptibility when a significant burden is observed patients versus control subjects. Such analyses might be particularly useful for candidate that are selected based on experiments other than genome-wide association (GWAS). We sought to determine whether rare variants non-GWAS identified from mouse models and human mendelian syndromes of hypertriglyceridemia (HTG) accumulate with polygenic adult-onset HTG.We resequenced...