title: Altered skeletal muscle fatty acid handling is associated with the degree of insulin resistance in overweight and obese humans.
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. [2H2]palmitate was infused i.v. to label VLDL-triacylglycerol (VLDL-TAG) and NEFA in the circulation, whereas [U-13C]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 (AUC0-4h: 0.57 ± 0.32 vs -0.43 ± 0.38 nmol [100 ml tissue]-1min-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.
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, PO Box 616, 6200 MD, Maastricht, the Netherlands. b.vanderkolk@maastrichtuniversity.nl.
authors.forename: Birgitta W
authors.initials: BW
authors.lastname: van der Kolk
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, PO Box 616, 6200 MD, Maastricht, the Netherlands.
authors.forename: Gijs H
authors.initials: GH
authors.lastname: Goossens
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, PO Box 616, 6200 MD, Maastricht, the Netherlands.
authors.forename: Johan W
authors.initials: JW
authors.lastname: Jocken
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, PO Box 616, 6200 MD, Maastricht, the Netherlands.
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
mesh_terms: D001835:Body Weight / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects; D005215:Fasting / Q000097:blood; D005227:Fatty Acids / Q000097:blood* / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology*; D050177:Overweight / Q000378:metabolism* / Q000503:physiopathology*; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides
keywords: Chylomicrons; Insulin resistance; Lipid metabolism; Skeletal muscle; VLDL