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Habegger, K.M. ; Donelan, E.* ; Abplanalp, W.* ; Al-Massadi, O.* ; Habegger, K.M.* ; Weber, J.* ; Ress, C.* ; Mansfeld, J.* ; Somvanshi, S.* ; Trivedi, C.* ; Keuper, M. ; Ograjsek, T. ; Striese, C. ; Cucuruz, S. ; Pfluger, P.T. ; Krishna, R.* ; Gordon, S.M.* ; Silva, R.A.* ; Luquet, S.* ; Castel, J.* ; Martinez, S.* ; D'Alessio, D.* ; Davidson, W.S.* ; Hofmann, S.M.

High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice.

Circulation 128, 2364-2371 (2013)
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BACKGROUND: Abnormal glucose metabolism is a central feature of disorders with increased rates of cardiovascular disease. Low levels of high-density lipoprotein (HDL) are a key predictor for cardiovascular disease. We used genetic mouse models with increased HDL levels (apolipoprotein A-I transgenic [apoA-I tg]) and reduced HDL levels (apoA-I-deficient [apoA-I ko]) to investigate whether HDL modulates mitochondrial bioenergetics in skeletal muscle. METHODS AND RESULTS: ApoA-I ko mice exhibited fasting hyperglycemia and impaired glucose tolerance test compared with wild-type mice. Mitochondria isolated from gastrocnemius muscle of apoA-I ko mice displayed markedly blunted ATP synthesis. Endurance capacity during exercise exhaustion test was impaired in apoA-I ko mice. HDL directly enhanced glucose oxidation by increasing glycolysis and mitochondrial respiration rate in C2C12 muscle cells. ApoA-I tg mice exhibited lower fasting glucose levels, improved glucose tolerance test, increased lactate levels, reduced fat mass, associated with protection against age-induced decline of endurance capacity compared with wild-type mice. Circulating levels of fibroblast growth factor 21, a novel biomarker for mitochondrial respiratory chain deficiencies and inhibitor of white adipose lipolysis, were significantly reduced in apoA-I tg mice. Consistent with an increase in glucose utilization of skeletal muscle, genetically increased HDL and apoA-I levels in mice prevented high-fat diet-induced impairment of glucose homeostasis. CONCLUSIONS: In view of impaired mitochondrial function and decreased HDL levels in type 2 diabetes mellitus, our findings indicate that HDL-raising therapies may preserve muscle mitochondrial function and address key aspects of type 2 diabetes mellitus beyond cardiovascular disease.  
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cellular Respiration ; Cholesterol ; Hdl ; Exercise ; Obesity; Apolipoprotein-a-i ; Reverse Cholesterol Transport ; Type-2 Diabetes-mellitus ; Insulin Sensitivity ; Glucose-metabolism ; Energy-expenditure ; Mitochondria ; Exercise ; Adipocytes ; Capacity
ISSN (print) / ISBN 0009-7322
e-ISSN 1524-4539
Zeitschrift Circulation
Quellenangaben Band: 128, Heft: 22, Seiten: 2364-2371 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Begutachtungsstatus Peer reviewed