Modulating Adipose Tissue Heme Biosynthesis To Promote Energy Expenditure in Obesity

At a Glance

The incidence of obesity has rapidly increased in Wisconsin and across the United States, and more than 65 percent of adults are overweight. Obese individuals are at increased risk for severe diseases including obesity-induced type 2 diabetes, cardiovascular disease, stroke, and cancer. Previous research has shown that low levels of ALAS1, an enzyme involved in heme biosynthesis, correlates with high body mass index (BMI) and higher risk of developing type 2 diabetes. For this project, researchers hypothesize that ALAS1, an enzyme involved in heme biosynthesis, may function as a metabolic sink to control the breakdown of amino acids in brown fat tissue. Successful completion of this project will allow researchers to better understand the role Alas1 plays in energy expenditure as it relates to obesity.

The Challenge

The incidence of obesity has rapidly increased in Wisconsin and across the United States, and more than 65 percent of adults are overweight. Obese individuals are at increased risk for severe diseases including obesity-induced type 2 diabetes, cardiovascular disease, stroke, and cancer. Previous research has shown that low levels of ALAS1, an enzyme involved in heme biosynthesis, correlates with high body mass index (BMI) and higher risk of developing type 2 diabetes.

Project Goals

Researchers hypothesize that ALAS1, an enzyme involved in heme biosynthesis, may function as a metabolic sink to control the breakdown of amino acids in brown fat tissue. The project will test this idea through two specific aims. First, the research team intends to characterize the mitochondrial dysfunction of ALAS1 deficient brown fat cells. Second, they plan to use mouse models to characterize the dysfunction of ALAS1 to better understand the impact of heme biosynthesis in brown fat cells