Genetic modification of dietary effects on nutrient distribution and metabolism

Genetics and Genomics; Endocrinology; Systems and Integrative Physiology; Nutrition

The aim of the project is to investigate effects of different diets on nutrient distribution and metabolism in key metabolic tissues and evaluate how individuals' genetic backgrounds modify effects.

Diet modification is a key approach to manage weight in obesity, treat type 2 diabetes, and prevent/ameliorate complications of obesity and diabetes (prominently cardiovascular disease). There is increasing awareness that different diets have diverse effects on metabolic parameters (including weight gain/loss, circulating metabolites), and that effects are modified by an individual’s genetic background. However, very little is known about the mechanisms mediating differential dietary effects on metabolism and which genetic variants modify diet responses in different individuals. The goal of this project is to investigate effects of different diets on nutrient distribution and metabolism in key metabolic tissues (adipose tissue, skeletal muscle and liver) and to identify genetic variants that modify nutrient distribution and metabolism in response to diets in different individuals. The plan is to feed genetically diverse mouse strains different common diets (including Western, Mediterranean and Vegan diets) and evaluate effects on nutrient distribution and metabolism using state-of-the art imaging techniques and established labeling methods. Association of genetic variants with nutrient differences in different tissues will be calculated. Clinical significance will subsequently be tested in patients undergoing dietary interventions for treatment of obesity, diabetes and complications of these diseases. This project will ideally engage the participation of experts in metabolism, population genetics/systems biology, and nutrition, and clinicians treating/managing patients with metabolic diseases. 

Please note that Susanna Keller will self-fund at $6,667.00

Desired outcomes

- The 3C program funds will be used to perform preliminary studies that support the concept and design of the project. Preliminary results obtained will then be used in a multi-PI R01 grant application to the NIH (responding to RFA PA-18-034 “Nutrigenetics and Nutrigenomics Approaches for Nutrition Research”). 

- The research is expected to ultimately provide crucial information towards designing personalized, genetically based, dietary approaches to treat metabolic diseases and associated complications.