Metabolic Characteristics of Primary Muscle Cells of Diet Sensitive and Diet Resistant Obese Patients

Abstract

In the Ottawa Hospital Weight Management Clinic, we have previously identified subpopulations of patients in the upper and lower quintiles for rate of weight loss, and characterized them as ‘obese diet sensitive’ (ODS) and ‘obese diet resistant’ (ODR) patient groups, respectively. Skeletal muscle is a major contributor to basal metabolic rate and mitochondrial proton leak in skeletal muscle can account for up to 50 % of resting oxygen consumption. The overall aim of this research is to explore differences in mitochondrial function in human primary myotubes from ODS and ODR subjects.

Subsets of ODS and ODR subjects (n = 9/group) who followed a hypocaloric clinical weight loss program at the Ottawa Weight Management Clinic consented to a muscle (vastus lateralis) biopsy. Human primary myoblasts obtained from biopsies were immunopurified and differentiated into myotubes. Mitochondrial function and distribution were compared in intact myotubes from ODS and ODR subjects.

Mitochondrial proton leak was significantly lower (p< 0.05) in ODR myotubes compared to ODS myotubes, independent of whether cells were differentiated in low or high glucose medium. In addition, in low glucose medium, ODR myotubes had higher MnSOD protein levels compared to ODS myotubes (p< 0.05). However, there were no significant differences in mitochondrial content, mitochondrial membrane potential, cellular ROS levels or ATP content between ODS and ODR myotubes. Overall, our in vitro mitochondrial proton leak results are consistent with our previous ex vivo results. Future research should examine the possibility that differences in proton leak between ODS and ODR groups may be related to mechanisms of cellular ROS regulation.