title: Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose.
abstract: Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [²H₂]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-(13)C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid content, their fractional synthetic rate (FSR) and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018) and peripheral insulin sensitivity tended to be reduced (p = 0.064) in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043), higher muscle TAG content (p = 0.025), higher saturation of FFA (p = 0.004), lower saturation of TAG (p = 0.017) and a tendency towards a lower TAG FSR (p = 0.073) and a lower saturation of DAG (p = 0.059) versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects.
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre<sup>+</sup>, Maastricht 6200 MD, The Netherlands. G.Goossens@maastrichtuniversity.nl.
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 Centre<sup>+</sup>, Maastricht 6200 MD, The Netherlands. c.moors@maastrichtuniversity.nl.
authors.forename: Chantalle C M
authors.initials: CC
authors.lastname: Moors
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre<sup>+</sup>, Maastricht 6200 MD, The Netherlands. j.jocken@maastrichtuniversity.nl.
authors.forename: Johan W E
authors.initials: JW
authors.lastname: Jocken
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam 1007 MB, The Netherlands. nj.vanderzijl@vumcl.nl.
authors.forename: Nynke J
authors.initials: NJ
authors.lastname: van der Zijl
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre<sup>+</sup>, Maastricht 6200 MD, The Netherlands. A.jans@maastrichtuniversity.nl.
authors.forename: Anneke
authors.initials: A
authors.lastname: Jans
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre<sup>+</sup>, Maastricht 6200 MD, The Netherlands. ellen.konings@maastrichtuniversity.nl.
authors.forename: Ellen
authors.initials: E
authors.lastname: Konings
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam 1007 MB, The Netherlands. m.diamant@vumc.nl.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.affiliation: Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre<sup>+</sup>, Maastricht 6200 MD, The Netherlands. e.blaak@maastrichtuniversity.nl.
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
mesh_terms: D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009426:Netherlands; D019308:Palmitic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004075:Diglycerides; D014280:Triglycerides; D019308:Palmitic Acid
keywords: impaired fasting glucose; impaired glucose tolerance; insulin resistance; lipid metabolism; skeletal muscle