{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T12:13:41Z","timestamp":1781180021124,"version":"3.54.1"},"reference-count":70,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Mayo Clinic Emslander Career Development"},{"name":"Mayo Clinic CTSA","award":["UL1 TR002377"],"award-info":[{"award-number":["UL1 TR002377"]}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Familial partial lipodystrophy (FPL), Dunnigan variety is characterized by skeletal muscle hypertrophy and insulin resistance besides fat loss from the extremities. The cause for the muscle hypertrophy and its functional consequences is not known.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To compare muscle strength and endurance, besides muscle protein synthesis rate between subjects with FPL and matched controls (n\u2005=\u20056 in each group). In addition, we studied skeletal muscle mitochondrial function and gene expression pattern to help understand the mechanisms for the observed differences.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Body composition by dual-energy X-ray absorptiometry, insulin sensitivity by minimal modelling, assessment of peak muscle strength and fatigue, skeletal muscle biopsy and calculation of muscle protein synthesis rate, mitochondrial respirometry, skeletal muscle transcriptome, proteome, and gene set enrichment analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Despite increased muscularity, FPL subjects did not demonstrate increased muscle strength but had earlier fatigue on chest press exercise. Decreased mitochondrial state 3 respiration in the presence of fatty acid substrate was noted, concurrent to elevated muscle lactate and decreased long-chain acylcarnitine. Based on gene transcriptome, there was significant downregulation of many critical metabolic pathways involved in mitochondrial biogenesis and function. Moreover, the overall pattern of gene expression was indicative of accelerated aging in FPL subjects. A lower muscle protein synthesis and downregulation of gene transcripts involved in muscle protein catabolism was observed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Increased muscularity in FPL is not due to increased muscle protein synthesis and is likely due to reduced muscle protein degradation. Impaired mitochondrial function and altered gene expression likely explain the metabolic abnormalities and skeletal muscle dysfunction in FPL subjects.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgab725","type":"journal-article","created":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T20:21:23Z","timestamp":1633551683000},"page":"346-362","source":"Crossref","is-referenced-by-count":10,"title":["Impaired Muscle Mitochondrial Function in Familial Partial Lipodystrophy"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9858-2832","authenticated-orcid":false,"given":"Vinaya","family":"Simha","sequence":"first","affiliation":[{"name":"Divisions of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R","family":"Lanza","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surendra","family":"Dasari","sequence":"additional","affiliation":[{"name":"Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A","family":"Klaus","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Le Brasseur","sequence":"additional","affiliation":[{"name":"Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Vuckovic","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello C","family":"Laurenti","sequence":"additional","affiliation":[{"name":"University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0169-6682","authenticated-orcid":false,"given":"Claudio","family":"Cobelli","sequence":"additional","affiliation":[{"name":"University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Port","sequence":"additional","affiliation":[{"name":"Radiology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K Sreekumaran","family":"Nair","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"issue":"12","key":"2022011806210059700_CIT0001","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1056\/NEJMra025261","article-title":"Acquired and inherited lipodystrophies","volume":"350","author":"Garg","year":"2004","journal-title":"N Engl J Med."},{"issue":"12","key":"2022011806210059700_CIT0002","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1210\/jc.2016-2466","article-title":"The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline","volume":"101","author":"Brown","year":"2016","journal-title":"J Clin Endocrinol Metab."},{"issue":"8","key":"2022011806210059700_CIT0003","doi-asserted-by":"crossref","first-page":"E1410","DOI":"10.1210\/jc.2013-1297","article-title":"Increased skeletal muscle volume in women with familial partial lipodystrophy, Dunnigan variety","volume":"98","author":"Ji","year":"2013","journal-title":"J Clin Endocrinol Metab."},{"issue":"9","key":"2022011806210059700_CIT0004","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."},{"issue":"18","key":"2022011806210059700_CIT0005","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1161\/01.CIR.103.18.2225","article-title":"Premature atherosclerosis associated with monogenic insulin resistance","volume":"103","author":"Hegele","year":"2001","journal-title":"Circulation."},{"issue":"7","key":"2022011806210059700_CIT0006","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.metabol.2009.02.027","article-title":"Inverse associations between muscle mass, strength, and the metabolic syndrome","volume":"58","author":"Atlantis","year":"2009","journal-title":"Metabolism."},{"issue":"9","key":"2022011806210059700_CIT0007","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1210\/jc.2011-0435","article-title":"Relative muscle mass is inversely associated with insulin resistance and prediabetes. 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