Reduced Incorporation of Fatty Acids Into Triacylglycerol in Myotubes From Obese Individuals With Type 2 Diabetes

Sparks, Lauren M., Bosma, Madeleen, Brouwers, Bram, van de Weijer, Tineke, Bilet, Lena, Schaart, Gert, Moonen-Kornips, Esther, Eichmann, Thomas O., Lass, Achim, Hesselink, Matthijs K. C., Schrauwen, Patrick

M.B. is financially supported by the NUTRIM-School for Nutrition, Toxicology and Metabolism and the Graduate School VLAG. This work received support from Austrian Science Fund grant P25193 (to A.L.). This work also was partially funded by a Vici grant (918.96.618) for innovative research from the Netherlands Organisation for Scientific Research (to P.S.).

Altered skeletal muscle lipid metabolism is a hallmark feature of type 2 diabetes (T2D). We investigated muscle lipid turnover in T2D versus BMI-matched control subjects (controls) and examined whether putative in vivo differences would be preserved in the myotubes. Male obese T2D individuals (n = 6) and BMI-matched controls (n = 6) underwent a hyperinsulinemic-euglycemic clamp, VO(2)max test, dual-energy X-ray absorptiometry scan, underwater weighing, and muscle biopsy of the vastus lateralis. C-14-palmitate and C-14-oleate oxidation rates and incorporation into lipids were measured in muscle tissue as well as in primary myotubes. Palmitate oxidation (controls: 0.99 +/- 0.17 nmol/mg protein; T2D: 0.53 +/- 0.07 nmol/mg protein; P = 0.03) and incorporation of fatty acids (FAs) into triacylglycerol (TAG) (controls: 0.45 +/- 0.13 nmol/mg protein; T2D: 0.11 +/- 0.02 nmol/mg protein; P = 0.047) were significantly reduced in muscle homogenates of T2D. These reductions were not retained for palmitate oxidation in primary myotubes (P = 0.38); however, incorporation of FAs into TAG was lower in T2D (P = 0.03 for oleate and P = 0.11 for palmitate), with a strong correlation of TAG incorporation between muscle tissue and primary myotubes (r = 0.848, P = 0.008). The data indicate that the ability to incorporate FAs into TAG is an intrinsic feature of human muscle cells that is reduced in individuals with T2D.

Reduced Incorporation of Fatty Acids Into Triacylglycerol in Myotubes From Obese Individuals With Type 2 Diabetes Article