Project 1 The nature of gene-by-diet interactions in obesity and other metabolic syndrome (MetSyn) traits is not well understood. Such interactions are likely to be key in understanding the worldwide ?epidemic of obesity?, particularly given the recent data implicating gut microbiota in cardio-metabolic traits. We propose a three- pronged approach to the problem. First, we will dissect gene-by-diet interactions affecting MetSyn traits (obesity, insulin resistance, fatty liver, plasma lipids) in a mouse population, the Hybrid Mouse Diversity Panel, that enables fine genetic mapping using association. Second, we will identify the underlying biochemical pathways using a systems genetics approach that allows us to follow the flow of information from DNA to transcriptome to proteome to metabolome to gut microbiome to MetSyn traits. Third, we will extend these findings to a human population, the METabolic Syndrome In Man (METSIM) study which consists of more than 10,000 men from Kuopio, Finland, that have been exquisitely characterized for MetSyn clinical traits, DNA variation and adipose tissue molecular phenotypes. The results will define mechanisms and genetic variations that underlie the striking divergent responses of individuals to unhealthy ?Western?-style diets rich in fat and sugar.

Public Health Relevance

Project 1 Diets rich in fat and refined carbohydrates underlie much of the current ?epidemic of obesity? and thereby much of atherosclerosis, diabetes, and heart failure. An understanding of the genetic factors mediating dietary responses should enable the development of improved diagnostics and therapeutic approaches.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL028481-34
Application #
9476303
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Liu, Lijuan
Project Start
Project End
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
34
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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