The overarching goal of this proposal is to determine whether DNA methylation of the mitochondrial DNA impairs mitochondrial function in insulin resistant states such as overweight/obesity and type 2 diabetes.
To determine whether differences in human skeletal muscle DNA methylation patterns in the mitochondrial and nuclear genome can explain the lower abundance of ETC and OXPHOS mRNA and protein observed in insulin resistant skeletal muscle of overweight/obese and type 2 diabetic participants. To determine whether patterns of human skeletal muscle DNA methylation in the mitochondrial and nuclear genome are predictive of ETC function. We will isolate skeletal muscle mitochondria from metabolically well-characterized lean insulin sensitive, overweight/obese insulin resistant nondiabetic and obese insulin resistant type 2 diabetic volunteers, and functionally evaluate each ETC complex (I - IV) and complex V (ATP synthase).
Study Type
OBSERVATIONAL
Enrollment
27
Participants will be recruited, and muscle biopsies will be obtained for methylation analyses and measuring mitochondrial function
Clinical and Translational Research Center (CaTS)
Tucson, Arizona, United States
Mitochondrial DNA methylation
Mitochondrial DNA methylation and D-loop of mitochondria is altered in insulin resistant states such as overweight/obesity and type 2 diabetes
Time frame: 3 years
Mitochondrial Function
The extent of mitochondrial function impairment in insulin resistant participants corresponds to the degree of methylation of the mitochondrial genome and D-loop
Time frame: 3 years
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