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Further elucidation of metabolic effects of exogenous leptin therapy will shed light on understanding leptin physiology in humans. Our objective was to utilize metabolomic profiling to examine the changes associated with administration of short-term metreleptin therapy in patients with lipodystrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>We conducted a pre-post-treatment study in 19 patients (75% female) with varying forms of lipodystrophy (congenital generalized lipodystrophy, n = 10; acquired generalized lipodystrophy, n = 1; familial partial lipodystrophy, n = 8) who received daily subcutaneous metreleptin injections for a period of 16 to 23 weeks. A 3-hour oral glucose tolerance test and body composition measurements were conducted before and after the treatment period, and fasting blood samples were used for metabolomic profiling. The study outcome aimed at measuring changes in physiologically relevant metabolites before and after leptin therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Metabolomic analysis revealed changes in pathways involving branched-chain amino acid metabolism, fatty acid oxidation, protein degradation, urea cycle, tryptophan metabolism, nucleotide catabolism, vitamin E, and steroid metabolism. Fold changes in pre- to post-treatment metabolite levels indicated increased breakdown of fatty acids, branched chain amino acids proteins, and nucleic acids.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Leptin replacement therapy has significant effects on important metabolic pathways implicated in patients with lipodystrophy. Continued metabolomic studies may provide further insight into the mechanisms of action of leptin replacement therapy and provide novel biomarkers of lipodystrophy.<\/jats:p><jats:p>Abbreviations: 1,5-AG, 1,5-anhydroglucitol; 11\u03b2HSD1, 11-\u03b2 hydroxysteroid dehydrogenase 1; BCAA, branched-chain amino acid; FFA, free fatty acid; GC-MS, gas chromatography mass spectrometry; IDO, indoleamine 2,3-dioxygenase; IFN-\u03b3, interferon-\u03b3; m\/z, mass to charge ratio; OGTT, oral glucose tolerance test; TDO, tryptophan 2,3-dioxygenase; TNF-\u03b1, tumor necrosis factor-\u03b1; UPLC-MS\/MS, ultra-performance liquid chromatography-tandem mass spectrometry.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jendso\/bvz022","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T16:01:08Z","timestamp":1574092868000},"source":"Crossref","is-referenced-by-count":14,"title":["Metabolomic Analysis of the Effects of Leptin Replacement Therapy in Patients with 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