{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:53:56Z","timestamp":1791921236348,"version":"4.3.4"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,11,26]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>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\u2013deficient [apoA-I ko]) to investigate whether HDL modulates mitochondrial bioenergetics in skeletal muscle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>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\u2013induced impairment of glucose homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.113.001551","type":"journal-article","created":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T22:53:19Z","timestamp":1383087199000},"page":"2364-2371","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":87,"title":["High-Density Lipoprotein Maintains Skeletal Muscle Function by Modulating Cellular Respiration in Mice"],"prefix":"10.1161","volume":"128","author":[{"given":"Maarit","family":"Lehti","sequence":"first","affiliation":[{"name":"From the Diabetes Research Department (IDO and IDR), Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, M\u00fcnchen\/Neuherberg, Germany (M.L., M.K., T.O., C.S., S.C., P.T.P., S.M.H.); Metabolic Diseases Institute, Division of Endocrinology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH (M.L., E.D., W.A., O.A.-M., K.M.H., J.W., C.R., J.M., S.S., C.T., R.K., S.M.G., R.A.G.D.S., D.D., W.S.D., S.M.H.); LIKES Research Center for Sport and Health Sciences,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Donelan","sequence":"additional","affiliation":[{"name":"From the Diabetes Research Department (IDO and IDR), Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, M\u00fcnchen\/Neuherberg, Germany (M.L., M.K., T.O., C.S., S.C., P.T.P., S.M.H.); Metabolic Diseases Institute, Division of Endocrinology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH (M.L., E.D., W.A., O.A.-M., K.M.H., J.W., C.R., J.M., S.S., C.T., R.K., S.M.G., R.A.G.D.S., D.D., W.S.D., S.M.H.); LIKES Research Center for Sport and Health Sciences,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Abplanalp","sequence":"additional","affiliation":[{"name":"From the Diabetes Research Department (IDO and IDR), Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, M\u00fcnchen\/Neuherberg, Germany (M.L., M.K., T.O., C.S., S.C., P.T.P., S.M.H.); Metabolic Diseases Institute, Division of Endocrinology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH (M.L., E.D., W.A., O.A.-M., K.M.H., J.W., C.R., J.M., S.S., C.T., R.K., S.M.G., R.A.G.D.S., D.D., W.S.D., S.M.H.); LIKES Research Center for Sport and Health Sciences,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Al-Massadi","sequence":"additional","affiliation":[{"name":"From the Diabetes Research Department (IDO and IDR), Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, M\u00fcnchen\/Neuherberg, Germany (M.L., M.K., T.O., C.S., S.C., P.T.P., S.M.H.); Metabolic Diseases Institute, Division of Endocrinology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH (M.L., E.D., W.A., O.A.-M., K.M.H., J.W., C.R., J.M., S.S., C.T., R.K., S.M.G., R.A.G.D.S., D.D., W.S.D., S.M.H.); LIKES Research Center for Sport and Health Sciences,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk M.","family":"Habegger","sequence":"additional","affiliation":[{"name":"From the Diabetes Research Department (IDO and IDR), Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, M\u00fcnchen\/Neuherberg, Germany (M.L., M.K., T.O., C.S., S.C., P.T.P., S.M.H.); Metabolic Diseases Institute, Division of Endocrinology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH (M.L., E.D., W.A., O.A.-M., K.M.H., J.W., C.R., J.M., S.S., C.T., R.K., S.M.G., R.A.G.D.S., D.D., W.S.D., S.M.H.); LIKES Research Center for Sport and Health Sciences,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Weber","sequence":"additional","affiliation":[{"name":"From the Diabetes Research Department (IDO and IDR), Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, M\u00fcnchen\/Neuherberg, Germany (M.L., M.K., T.O., C.S., S.C., P.T.P., S.M.H.); Metabolic Diseases Institute, Division of Endocrinology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH (M.L., E.D., W.A., O.A.-M., K.M.H., J.W., C.R., J.M., S.S., C.T., R.K., S.M.G., R.A.G.D.S., D.D., W.S.D., S.M.H.); LIKES Research Center for Sport and Health Sciences,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandler","family":"Ress","sequence":"additional","affiliation":[{"name":"From the Diabetes Research Department (IDO and IDR), Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, M\u00fcnchen\/Neuherberg, Germany (M.L., M.K., T.O., C.S., S.C., P.T.P., S.M.H.); Metabolic Diseases Institute, Division of Endocrinology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH (M.L., E.D., W.A., O.A.-M., K.M.H., J.W., C.R., J.M., S.S., C.T., R.K., S.M.G., R.A.G.D.S., D.D., W.S.D., S.M.H.); LIKES Research Center for Sport and Health Sciences,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Mansfeld","sequence":"additional","affiliation":[{"name":"From the Diabetes Research Department (IDO and IDR), Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, M\u00fcnchen\/Neuherberg, Germany (M.L., M.K., T.O., C.S., S.C., P.T.P., S.M.H.); Metabolic Diseases Institute, Division of Endocrinology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH (M.L., E.D., W.A., O.A.-M., K.M.H., J.W., C.R., J.M., S.S., C.T., R.K., S.M.G., R.A.G.D.S., D.D., W.S.D., S.M.H.); LIKES Research Center for Sport and Health Sciences,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonal","family":"Somvanshi","sequence":"additional","affiliation":[{"name":"From the Diabetes Research Department (IDO and IDR), Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, M\u00fcnchen\/Neuherberg, Germany (M.L., M.K., T.O., C.S., S.C., P.T.P., S.M.H.); 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Metabolic Diseases Institute, Division of Endocrinology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH (M.L., E.D., W.A., O.A.-M., K.M.H., J.W., C.R., J.M., S.S., C.T., R.K., S.M.G., R.A.G.D.S., D.D., W.S.D., S.M.H.); LIKES Research Center for Sport and Health Sciences,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teja","family":"Ograjsek","sequence":"additional","affiliation":[{"name":"From the Diabetes Research Department (IDO and IDR), Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, M\u00fcnchen\/Neuherberg, Germany (M.L., M.K., T.O., C.S., S.C., P.T.P., S.M.H.); Metabolic Diseases Institute, Division of Endocrinology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH (M.L., E.D., W.A., O.A.-M., K.M.H., J.W., C.R., J.M., S.S., C.T., R.K., S.M.G., R.A.G.D.S., D.D., W.S.D., S.M.H.); LIKES Research Center for Sport and Health Sciences,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Striese","sequence":"additional","affiliation":[{"name":"From the Diabetes Research Department (IDO and IDR), Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, M\u00fcnchen\/Neuherberg, Germany (M.L., M.K., T.O., C.S., S.C., P.T.P., S.M.H.); 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