title: A possible link between skeletal muscle mitochondrial efficiency and age-induced insulin resistance.
abstract: The transition from young to adult age is associated with decreased insulin sensitivity. To investigate whether changes in skeletal muscle mitochondrial function could be involved in the development of insulin resistance, we measured the oxidative capacity and energetic efficiency of subsarcolemmal and intermyofibrillar mitochondria isolated from the skeletal muscle of 60- and 180-day-old rats. Mitochondrial efficiency was tested by measuring the degree of thermodynamic coupling and optimal thermodynamic efficiency, as well as mitochondrial proton leak, which was determined in both the absence (basal) and the presence (fatty acid induced) of palmitate. Serum glucose, insulin, and HOMA index were also measured. The results show that in adult rats, concomitant with increased HOMA index, skeletal muscle mitochondria display higher respiratory capacity and energy efficiency. In fact, thermodynamic coupling and optimal thermodynamic efficiency significantly increased and fatty acid-induced proton leak was significantly lower in the skeletal muscle mitochondria from adult than in younger rats. A deleterious consequence of increased mitochondrial efficiency would be a reduced utilization of energy substrates, especially fatty acids, leading to intracellular triglyceride accumulation and lipotoxicity, thus contributing to the onset of skeletal muscle insulin resistance.
authors.affiliation: Department of General and Environmental Physiology, University of Naples, Italy. susiossa@unina.it.
authors.forename: Susanna
authors.initials: S
authors.lastname: Iossa
authors.forename: Maria Pina
authors.initials: MP
authors.lastname: Mollica
authors.forename: Lillà
authors.initials: L
authors.lastname: Lionetti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Crescenzo
authors.forename: Rosaria
authors.initials: R
authors.lastname: Tasso
authors.forename: Giovanna
authors.initials: G
authors.lastname: Liverini
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D012307:Risk Factors; D012508:Sarcolemma / Q000378:metabolism
chemical_list: D009243:NAD; D005182:Flavin-Adenine Dinucleotide