Altered skeletal muscle fatty acid handling is associated with the degree of insulin resistance in overweight and obese humans

Birgitta W. van der Kolk*, Gijs H. Goossens, Johan W. Jocken, Ellen E. Blaak

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

20 Citations (Web of Science)

Abstract

Disturbances in skeletal muscle fatty acid (FA) handling may contribute to the development and progression of whole-body insulin resistance (IR). In this study, we compared fasting and postprandial skeletal muscle FA handling in individuals with varying degrees of IR. Seventy-four overweight/obese participants (62 men) were divided into two groups based on the HOMA-IR median (3.35). Fasting and postprandial skeletal muscle FA handling were determined by combining the forearm muscle balance technique with stable isotopes. [H-2(2)]palmitate was infused i.v. to label VLDL-triacylglycerol (VLDL-TAG) and NEFA in the circulation, whereas [U-C-13]palmitate was incorporated in a high-saturated FA mixed-meal labelling chylomicron-TAG. Skeletal muscle biopsies were taken to assess intramuscular lipid content, fractional synthetic rate (FSR) and the transcriptional regulation of FA metabolism. Postprandial forearm muscle VLDL-TAG extraction was elevated in the high-IR vs the mild-IR group (AUC(0-4h): 0.57 +/- 0.32 vs -0.43 +/- 0.38 nmol [100 ml tissue](-1) min(-1), respectively, p = 0.045). Although no differences in skeletal muscle TAG, diacylglycerol, NEFA content and FSR were present between groups, the high-IR group showed increased saturation of the intramuscular NEFA pool (p = 0.039). This was accompanied by lower muscle GPAT1 (also known as GPAM) expression (p = 0.050). Participants with high-IR demonstrated increased postprandial skeletal muscle VLDL-TAG extraction and higher saturation of the intramuscular NEFA pool vs individuals with mild-IR. These data support the involvement of disturbances in skeletal muscle FA handling in the progression of whole-body IR.
Original languageEnglish
Pages (from-to)2686-2696
JournalDiabetologia
Volume59
Issue number12
DOIs
Publication statusPublished - Dec 2016

Keywords

  • Chylomicrons
  • Insulin resistance
  • Lipid metabolism
  • Skeletal muscle
  • VLDL

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