Effect of Leptin Administration on Circulating Apolipoprotein CIII levels in Patients With Lipodystrophy

Abstract

Context: Apolipoprotein CIII (apoCIII), an inhibitor of lipoprotein lipase, plays an important role in triglyceride metabolism. However, the role of apoCIII in hypertriglyceridemia in lipodystrophy and the effects of leptin replacement on apoCIII levels are unknown.

Objective: The objective of the study was to test the hypotheses that apoCIII is elevated in hypertriglyceridemic patients with lipodystrophy and that leptin replacement in these patients lowers circulating apoCIII.

Design, setting, study participants, intervention, and outcome measures: Using a post hoc cross-sectional case-control design, we compared serum apoCIII levels from patients with lipodystrophy not associated with HIV (n = 60) and age-, gender-, race-, and ethnicity-matched controls (n = 54) participating in ongoing studies at the National Institutes of Health. In a prospective, open-label, ongoing study, we studied the effects of 6–12 months of leptin replacement on apoCIII in lipodystrophy patients as an exploratory outcome.

Results: ApoCIII was higher in lipodystrophy patients (geometric mean [25th and 75th percentiles]) (23.9 mg/dL [14.6, 40.3]) compared with controls (14.9 mg/dL [12.3, 17.7]) (P < .0001). ApoCIII and triglyceride levels were positively correlated in patients with lipodystrophy (R = 0.72, P < .0001) and healthy controls (R = 0.6, P < .0001). Leptin replacement (6–12 mo) did not significantly alter apoCIII (before leptin: 23.4 mg/dL [14.5, 40.1]; after leptin: 21.4 mg/dL [16.7, 28.3]; P = .34).

Conclusions: Leptin replacement in lipodystrophy did not alter serum apoCIII levels. Elevated apoCIII may play a role in the hypertriglyceridemia of lipodystrophy independent of leptin deficiency and replacement.

Trial registration: ClinicalTrials.gov NCT00001987 NCT00025883 NCT00428987.

Figures

Figure 1.

apoCIII and TG levels and their correlation in lipodystrophy and overweight/obese controls. A, ApoCIII was significantly elevated in the lipodystrophy group compared with overweight/obese controls. I bars indicate SD. B, TGs were also significantly elevated in the lipodystrophy group vs overweight/obese controls. The horizontal bar is the geometric mean and I bars indicate 95% CI. C and D, There was a strong positive correlation between apoCIII and TGs in both lipodystrophy (panel C) and overweight/obese controls (panel D). Solid circles indicate lipodystrophy patients, and solid squares indicate overweight/obese controls.

Figure 2.

Correlation between changes in apoCIII and TGs in lipodystrophy patients after metreleptin. There was a positive correlation between changes in apoCIII and changes in TGs in lipodystrophy patients after leptin replacement for 6–12 months. Zero is marked with a dotted line on both axes.