Sudip Bajpeyi and Cassandra K. Myrland have equal contribution.
Lipid in skeletal muscle myotubes is associated to the donors' insulin sensitivity and physical activity phenotypes
Article first published online: 10 SEP 2013
Copyright © 2013 The Obesity Society
Volume 22, Issue 2, pages 426–434, February 2014
How to Cite
Bajpeyi, S., Myrland, C. K., Covington, J. D., Obanda, D., Cefalu, W. T., Smith, S. R., Rustan, A. C. and Ravussin, E. (2014), Lipid in skeletal muscle myotubes is associated to the donors' insulin sensitivity and physical activity phenotypes. Obesity, 22: 426–434. doi: 10.1002/oby.20556
Funding agencies: This word was supported by an unrestricted research grant from Novartis, Novartis Clinical Innovation Fund (to S.R.S.); an unrestricted research grant from Takeda Pharmaceuticals North America; NIH 1R01AG030226-01A2 (to S.R.S.) and was partially supported by NORC Center grant # 2P20DK072476-06 entitled “Nutritional Programming: Environmental and Molecular Interactions” sponsored by NIDDK and COBRE (NIH 2P20-RR021945). This work used the facilities of the Cell Biology and Bioimaging Core facilities that are supported in part by COBRE (NIH P20-RR021945) and CNRU (NIH 1P30-DK072476) center grants from the National Institutes of Health.
Clinicaltrials.gov registration numbers: NCT00402012, NCT00401791.
- Issue published online: 3 FEB 2014
- Article first published online: 10 SEP 2013
- Accepted manuscript online: 1 JUL 2013 08:11AM EST
- Manuscript Accepted: 17 JUN 2013
- Manuscript Received: 17 JUL 2012
This study investigated the relationship between in vitro lipid content in myotubes and in vivo whole body phenotypes of the donors such as insulin sensitivity, intramyocellular lipids (IMCL), physical activity, and oxidative capacity.
Design and Methods
Six physically active donors were compared to six sedentary lean and six T2DM. Lipid content was measured in tissues and myotubes by immunohistochemistry. Ceramides, triacylglycerols, and diacylglycerols (DAGs) were measured by LC-MS-MS and GC-FID. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp (80 mU min−1 m−2), maximal mitochondrial capacity (ATPmax) by 31P-MRS, physical fitness by VO2max and physical activity level (PAL) by accelerometers.
Myotubes cultured from physically active donors had higher lipid content (0.047 ± 0.003 vs. 0.032 ± 0.001 and 0.033 ± 0.001AU; P < 0.001) than myotubes from lean and T2DM donors. Lipid content in myotubes was not associated with IMCL in muscle tissue but importantly, correlated with in vivo measures of ATPmax (r = 0.74; P < 0.001), insulin sensitivity (r = 0.54; P < 0.05), type-I fibers (r = 0.50; P < 0.05), and PAL (r = 0.92; P < 0.0001). DAGs and ceramides in myotubes were inversely associated with insulin sensitivity (r = −0.55, r = −0.73; P < 0.05) and ATPmax (r = −0.74, r = −0.85; P < 0.01).
These results indicate that cultured human myotubes can be used in mechanistic studies to study the in vitro impact of interventions on phenotypes such as mitochondrial capacity, insulin sensitivity, and physical activity.