Altered skeletal muscle subsarcolemmal mitochondrial compartment during catch-up fat after caloric restriction.
An accelerated rate of fat recovery (catch-up fat) and insulin resistance are characteristic features of weight recovery after caloric restriction, with implications for the pathophysiology of catch-up growth and weight fluctuations. Using a previously described rat model of weight recovery in which catch-up fat and skeletal muscle insulin resistance have been linked to suppressed thermogenesis per se, we investigated alterations in mitochondrial energetics and oxidative stress in subsarcolemmal (SS) and intermyofibrillar (IMF) skeletal muscle mitochondria. After 2 weeks of semistarvation followed by 1 week of refeeding, the refed rats show persistent and selective reductions in SS mitochondrial mass (assessed from citrate synthase activity in tissue homogenate and isolated mitochondria) and oxidative capacity. Furthermore, the refed rats show, in both SS and IMF muscle mitochondria, a lower aconitase activity (whose inactivation is an index of increased reactive oxygen species [ROS]), associated with higher superoxide dismutase activity and increased proton leak. Taken together, these studies suggest that diminished skeletal muscle mitochondrial mass and function, specifically in the SS mitochondrial compartment, contribute to the high metabolic efficiency for catch-up fat after caloric restriction and underscore a potential link between diminished skeletal muscle SS mitochondrial energetics, increased ROS concentration, and insulin resistance during catch-up fat.
Crescenzo
Raffaella
R
Department of Biological Sciences, Section of Physiology, University of Naples, Naples, Italy.
Lionetti
Lillà
L
Mollica
Maria Pina
MP
Ferraro
Marialuisa
M
D'Andrea
Elvira
E
Mainieri
Davide
D
Dulloo
Abdul G
AG
Liverini
Giovanna
G
Iossa
Susanna
S
D000154:Aconitate Hydratase / Q000378:metabolism; D000273:Adipose Tissue; D000818:Animals; D015153:Blotting, Western; D001823:Body Composition; D031204:Caloric Restriction; D002352:Carrier Proteins / Q000032:analysis; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004734:Energy Metabolism; D005502:Food; D005508:Food Deprivation; D007333:Insulin Resistance; D007473:Ion Channels; D008297:Male; D008931:Mitochondria, Muscle / Q000737:chemistry / Q000201:enzymology / Q000648:ultrastructure*; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D018384:Oxidative Stress; D010101:Oxygen Consumption; D019308:Palmitic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis; D012508:Sarcolemma / Q000648:ultrastructure*; D013482:Superoxide Dismutase / Q000378:metabolism; D022722:Thermogenesis; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000071247:Uncoupling Protein 3; D019308:Palmitic Acid; D013482:Superoxide Dismutase; D002950:Citrate (si)-Synthase; D000154:Aconitate Hydratase