{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T16:20:35Z","timestamp":1784737235512,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01EO1501"],"award-info":[{"award-number":["01EO1501"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1052\/2, C06"],"award-info":[{"award-number":["SFB 1052\/2, C06"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Objective. Similar to obesity, lipodystrophy (LD) causes adipose tissue dysfunction and severe metabolic complications. Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor \u03b2 superfamily and is dysregulated in metabolic disease including obesity and diabetes mellitus. Circulating levels in LD and the impact of leptin treatment have not been investigated so far. Material and Methods. GDF15 serum levels were quantified in 60 LD patients without human immunodeficiency virus infection and 60 controls matched for age, gender, and body mass index. The impact of metreleptin treatment on circulating GDF15 was assessed in a subgroup of patients. GDF15 mRNA expression was determined in metabolic tissues of leptin-deficient lipodystrophic aP2-nSREBP1c-Tg mice, obese ob\/ob mice, and control C57Bl6 mice. Results. Median GDF15 serum concentrations were significantly higher in LD patients (819 ng\/L) as compared to the control group (415 ng\/L) (p &lt; 0.001). In multiple linear regression analysis, an independent and positive association remained between GDF15 on one hand and age, patient group, hemoglobin A1c, triglycerides, and C-reactive protein on the other hand. Moreover, there was an independent negative association between GFD15 and estimated glomerular filtration rate. Circulating GDF15 was not significantly affected by metreleptin treatment in LD patients. Gdf15 was upregulated in leptin-deficient lipodystrophic mice as compared to controls. Moreover, Gdf15 mRNA expression was downregulated by leptin treatment in lipodystrophic and obese animals. Conclusions. Serum concentrations of GDF15 are elevated in LD patients and independently associated with markers of metabolic dysfunction. Gdf15 expression is higher in lipodystrophic mice and downregulated by leptin treatment.<\/jats:p>","DOI":"10.3390\/ijms21197214","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T20:56:22Z","timestamp":1601412982000},"page":"7214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Increased Growth Differentiation Factor 15 in Patients with Hypoleptinemia-Associated Lipodystrophy"],"prefix":"10.3390","volume":"21","author":[{"given":"Susan","family":"Kralisch","sequence":"first","affiliation":[{"name":"Medical Department\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig, 04103 Leipzig, Germany"},{"name":"IFB AdiposityDiseases, Leipzig University Medical Center, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annett","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Medical Department\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Estrada-Kunz","sequence":"additional","affiliation":[{"name":"Medical Department\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Stumvoll","sequence":"additional","affiliation":[{"name":"Medical Department\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Fasshauer","sequence":"additional","affiliation":[{"name":"Medical Department\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig, 04103 Leipzig, Germany"},{"name":"IFB AdiposityDiseases, Leipzig University Medical Center, University of Leipzig, 04103 Leipzig, Germany"},{"name":"Department of Nutritional Sciences, University of Giessen, 35390 Gie\u03b2en, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"T\u00f6njes","sequence":"additional","affiliation":[{"name":"Medical Department\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstanze","family":"Miehle","sequence":"additional","affiliation":[{"name":"Medical Department\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5153","DOI":"10.3390\/nu6115153","article-title":"Obesity: Pathophysiology and intervention","volume":"6","author":"Zhang","year":"2014","journal-title":"Nutrients"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1210\/jc.2011-1159","article-title":"Clinical review#: Lipodystrophies: Genetic and acquired body fat disorders","volume":"96","author":"Garg","year":"2011","journal-title":"J. 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