title: Effects of acute lipid overload on skeletal muscle insulin resistance, metabolic flexibility, and mitochondrial performance.
abstract: We hypothesized that acute lipid-induced insulin resistance would be attenuated in high-oxidative muscle of lean trained (LT) endurance athletes due to their enhanced metabolic flexibility and mitochondrial capacity. Lean sedentary (LS), obese sedentary (OS), and LT participants completed two hyperinsulinemic euglycemic clamp studies with and without (glycerol control) the coinfusion of Intralipid. Metabolic flexibility was measured by indirect calorimetry as the oxidation of fatty acids and glucose during fasted and insulin-stimulated conditions, the latter with and without lipid oversupply. Muscle biopsies were obtained for mitochondrial and insulin-signaling studies. During hyperinsulinemia without lipid, glucose infusion rate (GIR) was lowest in OS due to lower rates of nonoxidative glucose disposal (NOGD), whereas state 4 respiration was increased in all groups. Lipid infusion reduced GIR similarly in all subjects and reduced state 4 respiration. However, in LT subjects, fat oxidation was higher with lipid oversupply, and although glucose oxidation was reduced, NOGD was better preserved compared with LS and OS subjects. Mitochondrial performance was positively associated with better NOGD and insulin sensitivity in both conditions. We conclude that enhanced mitochondrial performance with exercise is related to better metabolic flexibility and insulin sensitivity in response to lipid overload.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania and jjd8@pitt.edu.
authors.forename: John J
authors.initials: JJ
authors.lastname: Dubé
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Sanford/Burnham Medical Research Institute, Orlando, Florida.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Coen
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania and.
authors.forename: Giovanna
authors.initials: G
authors.lastname: DiStefano
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania and.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Chacon
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania and.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Helbling
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania and.
authors.forename: Marisa E
authors.initials: ME
authors.lastname: Desimone
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania and.
authors.forename: Maja
authors.initials: M
authors.lastname: Stafanovic-Racic
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania and.
authors.forename: Kazanna C
authors.initials: KC
authors.lastname: Hames
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania and.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Despines
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania and.
authors.forename: Frederico G S
authors.initials: FG
authors.lastname: Toledo
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Sanford/Burnham Medical Research Institute, Orlando, Florida.
authors.forename: Bret H
authors.initials: BH
authors.lastname: Goodpaster
mesh_terms: D000328:Adult; D019069:Cell Respiration / Q000187:drug effects; D004655:Emulsions / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000008:administration & dosage*; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010743:Phospholipids / Q000494:pharmacology; D013024:Soybean Oil / Q000494:pharmacology; D013997:Time Factors; D055815:Young Adult
chemical_list: D004655:Emulsions; D008055:Lipids; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil
keywords: lipids; mitochondria; skeletal muscle