Premium
Metabolic Flexibility is Impaired in Myotubes Derived from Severely Obese Humans
Author(s) -
Hinkley J Matthew,
Zou Kai,
Park Sanghee,
Zheng Donghai,
Houmard Joseph
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.824.14
Subject(s) - endocrinology , medicine , lipid oxidation , myogenesis , lipid metabolism , skeletal muscle , insulin resistance , beta oxidation , chemistry , insulin , metabolism , biology , biochemistry , antioxidant
Severe obesity (body mass index (BMI) > 40 kg/m 2 ) 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/m 2 ) and severely obese (BMI = 51.5 ± 1.8 kg/m 2 ) subjects, and differentiated into myotubes. In vitro metabolic flexibility was assessed by measuring 14 CO 2 production from radiolabeled 14 C‐oleic acid in myotubes treated for 24 hr with lipid (200 µM oleate : palmitate mixture). Treatment of myotubes with lipid induced a ~2.2‐fold increase in lipid oxidation in lean subjects, while the response from severely obese subjects was blunted (~66%). Furthermore, a negative correlation (R = ‐0.62) was evident between lipid‐induced increases in substrate oxidation and BMI, revealing that as body mass increases, in vitro metabolic flexibility becomes impaired. These data show that myotubes from severely obese subjects have a decreased ability to increase oxidation in the face of excess lipid, suggesting metabolic inflexibility observed at the whole body level with these subjects is preserved in vitro. SUPPORT: NIH DK56112.