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Leptin deficiency in GL leads to metabolic complications.

GL and Leptin

Leptin deficiency is the key pathogenic pathway underlying severe metabolic abnormalities in generalized lipodystrophy (GL)—with potential life-threatening implications.1,2

In normal physiology, leptin acts in the brain and periphery to regulate energy homeostasis and metabolic function in the body4,6

Adipose tissue produces leptin, a key regulator of metabolic function.5

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In GL, leptin deficiency leads to significant metabolic dysfunction.1,2

Metabolic abnormalities such as hyperphagia, insulin resistance, diabetes mellitus, and hypertriglyceridemia can lead to serious consequences in patients with GL.1,2

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1. Handelsman Y, Oral EA, Bloomgarden ZT, et al. The clinical approach to the detection of lipodystrophy—an AACE consensus statement. EndocrPract. 2013;19(1):107-116.doi:10.4158/endp.19.1.v767575m65p5mr06. 2. Brown RJ, Araujo-Vilar D, Cheung PT, et al. The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline. J Clin Endocrinol Metab. 2016;101(12):4500-4511. doi:10.1210/jc.2016-2466. 3. Van Maldergem L, Magré J, Khallouf TE, et al. Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy. J Med Genet. 2002;39(10):722-733. doi:10.1136/jmg.39.10.722. 4. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6): 2548-2556. doi:10.1210/jc.2004-0395. 5. Lago F, Dieguez C, Gómez-Reino J, Gualillo O. Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol. 2007;3(12):716-724. doi:10.1038/ncprheum0674. 6. Mantzoros CS, Magkos F, Brinkoetter M, et al. Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab. 2011;301(4):e567-e584. doi:10.1152/ ajpendo.00315.2011. 7. Kelesidis T, Kelesidis I, Chou S, Mantzoros CS. Narrative review:the role of leptin in human physiology: emerging clinical applications. Ann Intern Med. 2010;152(2):93-100. doi:10.1059/0003- 4819-152-2-201001190-00008. 8. Unger RH, OrciL. Lipoapoptosis: its mechanism and its diseases. BiochimBiophys Acta. 2002;1585(2-3):202-212. doi:10.1016/S1388-1981(02)00342-6. 9. Fiorenza CG, Chou SH, MantzorosCS. Lipodystrophy: pathophysiology and advances in treatment. Nat Rev Endocrinol. 2011;7(3):137-150. doi:10.1038/nrendo.2010.199. 10. Huang-Doran I, Sleigh A, Rochford JJ,O’Rahilly S, Savage DB. Lipodystrophy: metabolic insights from a rare disorder. J Endocrinol. 2010;207(3):245-255. doi:10.1677/JOE-10-0272. 11. Ginsberg HN. Insulin resistance and cardiovascular disease. J Clin Invest. 2000;106(4):453-458. doi:10.1172/JCI10762. 12. Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004;350(12):1220-1234. doi:10.1056/NEJMra025261. 13. Ferraria N, Pedrosa C, Amaral D, Lopes L. Berardinelli-Seip syndrome: highlight of treatment challenge [published online January 28,2013]. BMJ Case Rep. 2013. doi:10.1136/bcr-2012-007734. 14. Diabetes mellitus. Merck Manuals website. http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/diabetes_mellitus_and_disorders_of_carbohydrate_metabolism/diabetes_mellitus_dm.html?qt=HbA1c&alt=sh .Updated June 2014. Accessed March 3, 2017.