Short-term Effects of Leptin in People With Lipodystrophy

Summary

Background: \- Lipodystrophy is a condition where people do not have enough fat in the body. People with lipodystrophy can have problems such as diabetes or an enlarged liver. Researchers are looking at how leptin, a hormone produced by fat cells, can help people with these problems. Leptin helps control appetite and how the body stores food. Taking leptin can help people with lipodystrophy eat less food, which may help treat diabetes and other problems. To better understand how leptin works, researchers want to do an inpatient study on leptin treatment in people with lipodystrophy. Objectives: \- To study how leptin treatment affects lipodystrophy. Eligibility: \- Individuals between 14 and 70 years of age who have lipodystrophy. Design: * All participants will have a 19-day stay at the National Institutes of Health Clinical Center. One group of participants will have tests for 5 days before starting to take leptin. They will then take leptin for 2 weeks, and have more tests. The other group of participants will have tests for 5 days while taking leptin. They will then take stop taking leptin for 2 weeks, and have more tests, and then they will start taking leptin again. * Participants will have regular blood and urine tests during the visit. Some of the blood tests will look at insulin levels. Some will look at how the body metabolizes sugar and fat. Other tests will check hormone levels, especially of reproductive hormones. * During the visit, participants will spend 3 separate days in a metabolic chamber, a special room that measures how many calories the body uses. Urine samples will be collected during these stays. * Participants will also have several body imaging studies, including magnetic resonance imaging and a body composition scan. * Physical activity will be tested with an exercise bicycle and an electronic activity monitor. * Participants will be asked questions about hunger and comfort levels throughout the stay.

Timeline

Start

2013-01-26

Primary completion

2018-02-23

Completion

2018-02-23

Publications

• Background Ahima RS, Dushay J, Flier SN, Prabakaran D, Flier JS. Leptin accelerates the onset of puberty in normal female mice. J Clin Invest. 1997 Feb 1;99(3):391-5. doi: 10.1172/JCI119172.
• Background Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS. Role of leptin in the neuroendocrine response to fasting. Nature. 1996 Jul 18;382(6588):250-2. doi: 10.1038/382250a0.
• Background Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet. 1996 Mar;12(3):318-20. doi: 10.1038/ng0396-318.
• Quaye E, Chacko S, Startzell M, Brown RJ. Leptin Decreases Gluconeogenesis and Gluconeogenic Substrate Availability in Patients With Lipodystrophy. J Clin Endocrinol Metab. 2023 Dec 21;109(1):e209-e215. doi: 10.1210/clinem/dgad445.
• Meral R, Malandrino N, Walter M, Neidert AH, Muniyappa R, Oral EA, Brown RJ. Endogenous Leptin Concentrations Poorly Predict Metreleptin Response in Patients With Partial Lipodystrophy. J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1739-e1751. doi: 10.1210/clinem/dgab760.
• Nguyen ML, Sachdev V, Burklow TR, Li W, Startzell M, Auh S, Brown RJ. Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy. J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4327-e4339. doi: 10.1210/clinem/dgab499.
• Grover A, Quaye E, Brychta RJ, Christensen J, Startzell MS, Meehan CA, Valencia A, Marshall B, Chen KY, Brown RJ. Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy. J Clin Endocrinol Metab. 2021 Sep 27;106(10):e4163-e4178. doi: 10.1210/clinem/dgab269.
• Baykal AP, Parks EJ, Shamburek R, Syed-Abdul MM, Chacko S, Cochran E, Startzell M, Gharib AM, Ouwerkerk R, Abd-Elmoniem KZ, Walter PJ, Walter M, Muniyappa R, Chung ST, Brown RJ. Leptin decreases de novo lipogenesis in patients with lipodystrophy. JCI Insight. 2020 Jul 23;5(14):e137180. doi: 10.1172/jci.insight.137180.
• Sekizkardes H, Chung ST, Chacko S, Haymond MW, Startzell M, Walter M, Walter PJ, Lightbourne M, Brown RJ. Free fatty acid processing diverges in human pathologic insulin resistance conditions. J Clin Invest. 2020 Jul 1;130(7):3592-3602. doi: 10.1172/JCI135431.
• Sekizkardes H, Cochran E, Malandrino N, Garg A, Brown RJ. Efficacy of Metreleptin Treatment in Familial Partial Lipodystrophy Due to PPARG vs LMNA Pathogenic Variants. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3068-3076. doi: 10.1210/jc.2018-02787.
• Brown RJ, Valencia A, Startzell M, Cochran E, Walter PJ, Garraffo HM, Cai H, Gharib AM, Ouwerkerk R, Courville AB, Bernstein S, Brychta RJ, Chen KY, Walter M, Auh S, Gorden P. Metreleptin-mediated improvements in insulin sensitivity are independent of food intake in humans with lipodystrophy. J Clin Invest. 2018 Aug 1;128(8):3504-3516. doi: 10.1172/JCI95476. Epub 2018 Jul 16.
• Brown RJ, Meehan CA, Cochran E, Rother KI, Kleiner DE, Walter M, Gorden P. Effects of Metreleptin in Pediatric Patients With Lipodystrophy. J Clin Endocrinol Metab. 2017 May 1;102(5):1511-1519. doi: 10.1210/jc.2016-3628.

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