Metabolic Flexibility is Impaired in Myotubes Derived from Severely Obese Humans

Abstract

Severe obesity (body mass index (BMI) > 40 kg/m2) is associated with various metabolic derangements, including impaired lipid oxidation and insulin resistance. The impairments in lipid oxidation and insulin action are retained in primary skeletal muscle cells, suggesting whole body derangements in metabolism are imprinted at the level of the cell; however, it is uncertain whether alterations in metabolic flexibility (the ability to switch substrate oxidation in the face of increased supply) are also preserved. The goal of this study was to examine alterations in lipid oxidation in the face of an increased substrate supply in vitro. To determine this, primary skeletal muscle cells were isolated from muscle biopsies obtained from lean (BMI = 24.7 ± 0.7 kg/m2) and severely obese (BMI = 51.5 ± 1.8 kg/m2) subjects, and differentiated into myotubes. In vitro metabolic flexibility was assessed by measuring 14CO2 production from radiolabeled 14C-oleic acid in myotubes treated for 24 hr with lipid (200 µM oleate :...