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ABSTRACT: 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.
SUBMITTER: Muniyappa R
PROVIDER: S-EPMC5433252 | biostudies-literature | 2017 Mar - Apr
REPOSITORIES: biostudies-literature
Muniyappa Ranganath R Abel Brent S BS Asthana Asha A Walter Mary F MF Cochran Elaine K EK Remaley Alan T AT Skarulis Monica C MC Gorden Phillip P Brown Rebecca J RJ
Journal of clinical lipidology 20170224 2
<h4>Background</h4>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.<h4>Objective</h4>To examine if ANGPTL3/4 levels are elevated in patients with g ...[more]