{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T01:25:07Z","timestamp":1770081907072,"version":"3.49.0"},"reference-count":39,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Context: Type 2 familial partial lipodystrophy (FPLD) is an autosomal-dominant lamin A\/C-related disease associated with exercise intolerance, muscular pain, and insulin resistance. The symptoms may all be explained by defective metabolism; however, metabolism at the tissue level has not been investigated.<\/jats:p>\n               <jats:p>Objective: We hypothesized that in FPLD, insulin resistance and impaired aerobic exercise capacity are explained by a common underlying mechanism, presumably a muscular metabolic defect.<\/jats:p>\n               <jats:p>Patients and Methods: Carbohydrate and lipid metabolism was studied on 10 FPLD patients, one patient with limb-girdle muscular dystrophy (LGMD1B, a different lamin A\/C disease), and 10 healthy control subjects before and during an oral glucose tolerance test by indirect calorimetry and im microdialysis. Muscle biopsies were taken for in vitro studies.<\/jats:p>\n               <jats:p>Results: We observed marked increased skeletal muscle fatty acid \u03b2-oxidation rate in vitro and in vivo, even after glucose ingestion in FPLD patients. However, fatty acid oxidation was largely incomplete and accompanied by increased ketogenesis. The lipid oxidation abnormality was associated with impaired glucose disposition through reduction in glucose oxidation, rather than decreased cellular glucose uptake. A microarray showed down-regulation of complex I respiratory chain, glycolysis, and nuclear transport genes. Although not overtly insulin resistant, the LGMD1B patient showed similar metabolic derangements as the FPLD patients.<\/jats:p>\n               <jats:p>Conclusions: Our study suggests imbalance between lipid oxidation and oxidative glucose metabolism in FPLD and LGMD1B patients. The observation suggests an intrinsic defect in skeletal muscle metabolism due to lamin A\/C dysfunction. The metabolic FPLD phenotype likely results from this intrinsic defect combined with lipodystrophic \u201clipid pressure\u201d due to decreased adipose tissue lipid storage capacity.<\/jats:p>","DOI":"10.1210\/jc.2009-1293","type":"journal-article","created":{"date-parts":[[2010,2,4]],"date-time":"2010-02-04T02:10:43Z","timestamp":1265249443000},"page":"1634-1643","source":"Crossref","is-referenced-by-count":40,"title":["LMNA Mutations, Skeletal Muscle Lipid Metabolism, and Insulin Resistance"],"prefix":"10.1210","volume":"95","author":[{"given":"Michael","family":"Boschmann","sequence":"first","affiliation":[{"name":"Franz-Volhard Clinical Research Center at the Experimental and Clinical Research Center (M.B., F.A., K.G., G.R., A.M., K.D., A.K., F.C.L.), University Hospital Charite\u0301 Campus Buch and HELIOS Klinikum-Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Engeli","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology (S.E., J.J.), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cedric","family":"Moro","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center (C.M., S.R.S.), Louisiana State University System, Baton Rouge, Louisiana 70808"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelika","family":"Luedtke","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Anatomy and Cell Biology (A.L.), College of Physicians and Surgeons, Columbia University, New York, New York 10032"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frauke","family":"Adams","sequence":"additional","affiliation":[{"name":"Franz-Volhard Clinical Research Center at the Experimental and Clinical Research Center (M.B., F.A., K.G., G.R., A.M., K.D., A.K., F.C.L.), University Hospital Charite\u0301 Campus Buch and HELIOS Klinikum-Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Gorzelniak","sequence":"additional","affiliation":[{"name":"Franz-Volhard Clinical Research Center at the Experimental and Clinical Research Center (M.B., F.A., K.G., G.R., A.M., K.D., A.K., F.C.L.), University Hospital Charite\u0301 Campus Buch and HELIOS Klinikum-Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Rahn","sequence":"additional","affiliation":[{"name":"Franz-Volhard Clinical Research Center at the Experimental and Clinical Research Center (M.B., F.A., K.G., G.R., A.M., K.D., A.K., F.C.L.), University Hospital Charite\u0301 Campus Buch and HELIOS Klinikum-Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Ma\u0308hler","sequence":"additional","affiliation":[{"name":"Franz-Volhard Clinical Research Center at the Experimental and Clinical Research Center (M.B., F.A., K.G., G.R., A.M., K.D., A.K., F.C.L.), University Hospital Charite\u0301 Campus Buch and HELIOS Klinikum-Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Dobberstein","sequence":"additional","affiliation":[{"name":"Franz-Volhard Clinical Research Center at the Experimental and Clinical Research Center (M.B., F.A., K.G., G.R., A.M., K.D., A.K., F.C.L.), University Hospital Charite\u0301 Campus Buch and HELIOS Klinikum-Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antje","family":"Kru\u0308ger","sequence":"additional","affiliation":[{"name":"Franz-Volhard Clinical Research Center at the Experimental and Clinical Research Center (M.B., F.A., K.G., G.R., A.M., K.D., A.K., F.C.L.), University Hospital Charite\u0301 Campus Buch and HELIOS Klinikum-Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saskia","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Myology Research Group at the Experimental & Clinical Research Center (S.Sc., S.Sp.), University Hospital Charite\u0301 Campus Buch, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Spuler","sequence":"additional","affiliation":[{"name":"Myology Research Group at the Experimental & Clinical Research Center (S.Sc., S.Sp.), University Hospital Charite\u0301 Campus Buch, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friedrich C.","family":"Luft","sequence":"additional","affiliation":[{"name":"Franz-Volhard Clinical Research Center at the Experimental and Clinical Research Center (M.B., F.A., K.G., G.R., A.M., K.D., A.K., F.C.L.), University Hospital Charite\u0301 Campus Buch and HELIOS Klinikum-Berlin, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center (C.M., S.R.S.), Louisiana State University System, Baton Rouge, Louisiana 70808"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hartmut H.-J.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine B (H.H.-J.S.), Westfa\u0308lische Wilhelms-Universita\u0308t Mu\u0308nster, 48149 Mu\u0308nster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Jordan","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology (S.E., J.J.), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071613285391300_R1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/hmg\/9.1.109","article-title":"Nuclear lamin A\/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy","volume":"9","author":"Cao","year":"2000","journal-title":"Hum Mol Genet"},{"key":"2020071613285391300_R2","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1086\/302836","article-title":"Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A\/C","volume":"66","author":"Speckman","year":"2000","journal-title":"Am J Hum Genet"},{"key":"2020071613285391300_R3","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/72807","article-title":"LMNA, encoding lamin A\/C, is mutated in partial lipodystrophy","volume":"24","author":"Shackleton","year":"2000","journal-title":"Nat Genet"},{"key":"2020071613285391300_R4","first-page":"3431","article-title":"Heterogeneity of nuclear lamin A mutations in Dunnigan-type familial partial lipodystrophy","volume":"85","author":"Hegele","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613285391300_R5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrm1550","article-title":"The nuclear lamina comes of age","volume":"6","author":"Gruenbaum","year":"2005","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2020071613285391300_R6","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/323560a0","article-title":"The nuclear lamina is a meshwork of intermediate-type filaments","volume":"323","author":"Aebi","year":"1986","journal-title":"Nature"},{"key":"2020071613285391300_R7","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1615\/CritRevEukarGeneExpr.v15.i4.10","article-title":"Linkage of lamins to fidelity of gene transcription","volume":"15","author":"Maraldi","year":"2005","journal-title":"Crit Rev Eukaryot Gene Expr"},{"key":"2020071613285391300_R8","first-page":"170","article-title":"Adipose tissue distribution pattern in patients with familial partial lipodystrophy (Dunnigan variety)","volume":"84","author":"Garg","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613285391300_R9","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1046\/j.1464-5491.2002.00796.x","article-title":"Post-mortem findings in familial partial lipodystrophy, Dunnigan variety","volume":"19","author":"Haque","year":"2002","journal-title":"Diabet Med"},{"key":"2020071613285391300_R10","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1111\/j.1572-0241.2005.00234.x","article-title":"Hepatic steatosis in Dunnigan-type familial partial lipodystrophy","volume":"100","author":"Lu\u0308dtke","year":"2005","journal-title":"Am J Gastroenterol"},{"key":"2020071613285391300_R11","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1212\/01.wnl.0000255939.73424.f8","article-title":"Muscle and nerve pathology in Dunnigan familial partial lipodystrophy","volume":"68","author":"Spuler","year":"2007","journal-title":"Neurology"},{"key":"2020071613285391300_R12","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00415-005-0719-x","article-title":"A new LMNA mutation causing limb girdle muscular dystrophy 1B","volume":"252","author":"Spuler","year":"2005","journal-title":"J Neurol"},{"key":"2020071613285391300_R13","doi-asserted-by":"crossref","first-page":"4835","DOI":"10.1210\/jc.2007-0654","article-title":"New metabolic phenotypes in laminopathies: LMNA mutations in patients with severe metabolic syndrome","volume":"92","author":"Decaudain","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613285391300_R14","first-page":"2803","article-title":"Interaction between \u03b2-adrenergic receptor stimulation and nitric oxide release on tissue perfusion and metabolism","volume":"86","author":"Jordan","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613285391300_R15","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1161\/01.HYP.0000171477.63859.b2","article-title":"Adipose tissue metabolism and CD11b expression on monocytes in obese hypertensives","volume":"46","author":"Boschmann","year":"2005","journal-title":"Hypertension"},{"key":"2020071613285391300_R16","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1152\/jappl.1995.79.2.638","article-title":"Muscle blood flow in cats: comparison of microdialysis ethanol technique with direct measurement","volume":"79","author":"Hickner","year":"1995","journal-title":"J Appl Physiol"},{"key":"2020071613285391300_R17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1042\/cs0860015","article-title":"Muscle blood flow during intermittent exercise: comparison of the microdialysis ethanol technique and 133Xe clearance","volume":"86","author":"Hickner","year":"1994","journal-title":"Clin Sci (Lond)"},{"key":"2020071613285391300_R18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/0160-5402(91)90021-V","article-title":"A comparison between three methods for estimation of extracellular concentrations of exogenous and endogenous compounds by microdialysis","volume":"25","author":"Sta\u030ahle","year":"1991","journal-title":"J Pharmacol Methods"},{"key":"2020071613285391300_R19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cmet.2007.10.013","article-title":"Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance","volume":"7","author":"Koves","year":"2008","journal-title":"Cell Metab"},{"key":"2020071613285391300_R20","doi-asserted-by":"crossref","first-page":"609","DOI":"10.3109\/00365517509095787","article-title":"Percutaneous needle biopsy of skeletal muscle in physiological and clinical research","volume":"35","author":"Bergstrom","year":"1975","journal-title":"Scand J Clin Lab Invest"},{"key":"2020071613285391300_R21","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1172\/JCI24332","article-title":"Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor","volume":"115","author":"Ukropcova","year":"2005","journal-title":"J Clin Invest"},{"key":"2020071613285391300_R22","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.cmet.2005.09.002","article-title":"Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans","volume":"2","author":"Hulver","year":"2005","journal-title":"Cell Metab"},{"key":"2020071613285391300_R23","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.2337\/diabetes.54.7.1926","article-title":"A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle","volume":"54","author":"Sparks","year":"2005","journal-title":"Diabetes"},{"key":"2020071613285391300_R24","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1101\/gr.772403","article-title":"PANTHER: a library of protein families and subfamilies indexed by function","volume":"13","author":"Thomas","year":"2003","journal-title":"Genome Res"},{"key":"2020071613285391300_R25","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1042\/bst0280182","article-title":"The carnitine acyltransferases: modulators of acyl-CoA-dependent reactions","volume":"28","author":"Ramsay","year":"2000","journal-title":"Biochem Soc Trans"},{"key":"2020071613285391300_R26","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.0954-6820.1976.tb08218.x","article-title":"Metabolism of mono- and diacylglycerols in subcutaneous adipose tissue of obese and normal-weight subjects","volume":"200","author":"Arner","year":"1976","journal-title":"Acta Med Scand"},{"key":"2020071613285391300_R27","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1161\/01.HYP.0000042665.85720.A0","article-title":"Tissue-specific response to interstitial angiotensin II in humans","volume":"41","author":"Boschmann","year":"2003","journal-title":"Hypertension"},{"key":"2020071613285391300_R28","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.2337\/db06-0616","article-title":"Retinol-binding protein 4 in human obesity","volume":"55","author":"Janke","year":"2006","journal-title":"Diabetes"},{"key":"2020071613285391300_R29","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.4161\/cc.8.10.8499","article-title":"Lamin complexes in the nuclear interior control progenitor cell proliferation and tissue homeostasis","volume":"8","author":"Naetar","year":"2009","journal-title":"Cell Cycle"},{"key":"2020071613285391300_R30","doi-asserted-by":"crossref","first-page":"E274","DOI":"10.1152\/ajpendo.00391.2001","article-title":"Intramyocellular lipid accumulation and reduced whole body lipid oxidation in HIV lipodystrophy","volume":"284","author":"Luzi","year":"2003","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2020071613285391300_R31","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1152\/japplphysiol.00797.2005","article-title":"Increased intramyocellular lipid accumulation in HIV-infected women with fat redistribution","volume":"100","author":"Torriani","year":"2006","journal-title":"J Appl Physiol"},{"key":"2020071613285391300_R32","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1042\/bst0311152","article-title":"Fatty acid-induced insulin resistance: role of insulin receptor substrate 1 serine phosphorylation in the retroregulation of insulin signalling","volume":"31","author":"Le Marchand-Brustel","year":"2003","journal-title":"Biochem Soc Trans"},{"key":"2020071613285391300_R33","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/(SICI)1099-0895(199812)14:4<263::AID-DMR233>3.0.CO;2-C","article-title":"Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years","volume":"14","author":"Randle","year":"1998","journal-title":"Diabetes Metab Rev"},{"key":"2020071613285391300_R34","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1056\/NEJMoa031314","article-title":"Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes","volume":"350","author":"Petersen","year":"2004","journal-title":"N Engl J Med"},{"key":"2020071613285391300_R35","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.2337\/diabetes.51.10.2944","article-title":"Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes","volume":"51","author":"Kelley","year":"2002","journal-title":"Diabetes"},{"key":"2020071613285391300_R36","doi-asserted-by":"crossref","first-page":"8","DOI":"10.2337\/diabetes.54.1.8","article-title":"Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes","volume":"54","author":"Ritov","year":"2005","journal-title":"Diabetes"},{"key":"2020071613285391300_R37","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng1180","article-title":"PGC-1\u03b1-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes","volume":"34","author":"Mootha","year":"2003","journal-title":"Nat Genet"},{"key":"2020071613285391300_R38","doi-asserted-by":"crossref","first-page":"8466","DOI":"10.1073\/pnas.1032913100","article-title":"Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1","volume":"100","author":"Patti","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613285391300_R39","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.2337\/db08-1096","article-title":"Paradoxical coupling of triglyceride synthesis and fatty acid oxidation in skeletal muscle overexpressing DGAT1","volume":"58","author":"Liu","year":"2009","journal-title":"Diabetes"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/95\/4\/1634\/10780515\/jcem1634.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/95\/4\/1634\/10780515\/jcem1634.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T23:55:16Z","timestamp":1594943716000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/95\/4\/1634\/2596695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4,1]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2010,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2009-1293","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4,1]]}}}