Metreleptin therapy lowers plasma angiopoietin-like protein 3 in patients with generalized lipodystrophy.

Autor: Muniyappa R; Diabetes, Endocrinology, and Obesity Branch, NIDDK, NIH, Bethesda, MD, USA. Electronic address: muniyapr@mail.nih.gov., Abel BS; Diabetes, Endocrinology, and Obesity Branch, NIDDK, NIH, Bethesda, MD, USA., Asthana A; Diabetes, Endocrinology, and Obesity Branch, NIDDK, NIH, Bethesda, MD, USA., Walter MF; Clinical Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA., Cochran EK; Diabetes, Endocrinology, and Obesity Branch, NIDDK, NIH, Bethesda, MD, USA., Remaley AT; Lipoprotein Metabolism Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Skarulis MC; Diabetes, Endocrinology, and Obesity Branch, NIDDK, NIH, Bethesda, MD, USA., Gorden P; Diabetes, Endocrinology, and Obesity Branch, NIDDK, NIH, Bethesda, MD, USA., Brown RJ; Diabetes, Endocrinology, and Obesity Branch, NIDDK, NIH, Bethesda, MD, USA.
Jazyk: angličtina
Zdroj: Journal of clinical lipidology [J Clin Lipidol] 2017 Mar - Apr; Vol. 11 (2), pp. 543-550. Date of Electronic Publication: 2017 Feb 24.
DOI: 10.1016/j.jacl.2017.02.002
Abstrakt: Background: Reduced triglyceride clearance due to impaired lipoprotein lipase-mediated lipolysis contributes to severe hypertriglyceridemia in lipodystrophy. Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) impair clearance of triglycerides by inhibiting lipoprotein lipase. Whether circulating ANGPTL3/4 levels are altered in lipodystrophy and the effects of leptin replacement on these ANGPTLs are unknown.
Objective: To examine if ANGPTL3/4 levels are elevated in patients with generalized lipodystrophy and assess the effects of leptin replacement on these ANGPTLs.
Methods: Preleptin treatment plasma levels of ANGPTLs in patients with generalized lipodystrophy (n = 22) were compared with healthy controls (n = 39) using a post hoc case-control study design. In a prospective open-label study, we studied the effects of metreleptin therapy (16-32 weeks) on plasma ANGPTL3/4 in patients with generalized lipodystrophy.
Results: Plasma ANGPTL3 (geometric mean [95% confidence interval]; 223 [182-275] vs 174 ng/mL [160-189], P = .02) but not ANGPTL4 levels (55 [37-81] vs 44 ng/mL [37-52], P = .26) were higher in patients with lipodystrophy compared with healthy controls. There was a significant decrease in total cholesterol, triglycerides, and glycosylated hemoglobin (A1C) levels following metreleptin therapy. After metreleptin, ANGPTL3 concentrations decreased significantly (223 [182-275] vs 175 ng/mL [144-214], P = .01) with no change in ANGPTL4 (55 [37-81] vs 48 ng/mL [32-73], P = .11).
Conclusions: These findings suggest that elevated plasma levels of ANGPTL3 in leptin-deficient states is attenuated with leptin therapy.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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