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2017 ; 11
(2
): 543-550
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Metreleptin therapy lowers plasma angiopoietin-like protein 3 in patients with
generalized lipodystrophy
#MMPMID28502512
Muniyappa R
; Abel BS
; Asthana A
; Walter MF
; Cochran EK
; Remaley AT
; Skarulis MC
; Gorden P
; Brown RJ
J Clin Lipidol
2017[Mar]; 11
(2
): 543-550
PMID28502512
show ga
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.
|Adult
[MESH]
|Angiopoietin-Like Protein 3
[MESH]
|Angiopoietin-Like Protein 4/blood
[MESH]
|Angiopoietin-like Proteins/*blood
[MESH]
|Case-Control Studies
[MESH]
|Female
[MESH]
|Humans
[MESH]
|Leptin/*analogs & derivatives/pharmacology/therapeutic use
[MESH]
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