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Apolipoprotein CIII and Angiopoietin-like Protein 8 are Elevated in Lipodystrophy and Decrease after Metreleptin
- Source :
- J Endocr Soc
- Publication Year :
- 2020
- Publisher :
- The Endocrine Society, 2020.
-
Abstract
- Context Lipodystrophy syndromes cause hypertriglyceridemia that improves with leptin treatment using metreleptin. Mechanisms causing hypertriglyceridemia and improvements after metreleptin are incompletely understood. Objective Determine relationship of circulating lipoprotein lipase (LPL) modulators with hypertriglyceridemia in healthy controls and in patients with lipodystrophy before and after metreleptin. Methods Cross-sectional comparison of patients with lipodystrophy (generalized lipodystrophy n = 3; partial lipodystrophy n = 11) vs age/sex-matched healthy controls (n = 28), and longitudinal analyses in patients before and after 2 weeks and 6 months of metreleptin. The study was carried out at the National Institutes of Health, Bethesda, Maryland. Outcomes were LPL stimulators apolipoprotein (apo) C-II and apoA-V and inhibitors apoC-III and angiopoietin-like proteins (ANGPTLs) 3, 4, and 8; ex vivo activation of LPL by plasma. Results Patients with lipodystrophy were hypertriglyceridemic and had higher levels of all LPL stimulators and inhibitors vs controls except for ANGPTL4, with >300-fold higher ANGPTL8, 4-fold higher apoC-III, 3.5-fold higher apoC-II, 1.9-fold higher apoA-V, 1.6-fold higher ANGPTL3 (P < .05 for all). At baseline, all LPL modulators except ANGPLT4 positively correlated with triglycerides. Metreleptin decreased apoC-II and apoC-III after 2 weeks and 6 months, and decreased ANGPTL8 after 6 months (P < 0.05 for all). Plasma from patients with lipodystrophy caused higher ex vivo LPL activation vs hypertriglyceridemic control plasma (P < .0001), which did not change after metreleptin. Conclusion Elevations in LPL inhibitors apoC-III and ANGPTL8 may contribute to hypertriglyceridemia in lipodystrophy, and may mediate reductions in circulating and hepatic triglycerides after metreleptin. These therefore are strong candidates for therapies to lower triglycerides in these patients.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Apolipoprotein B
Endocrinology, Diabetes and Metabolism
030204 cardiovascular system & hematology
03 medical and health sciences
Metreleptin
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Clinical Research Articles
Lipoprotein lipase
biology
business.industry
Generalized lipodystrophy
Leptin
Partial Lipodystrophy
Hypertriglyceridemia
nutritional and metabolic diseases
medicine.disease
030104 developmental biology
Endocrinology
chemistry
biology.protein
lipids (amino acids, peptides, and proteins)
Lipodystrophy
business
Subjects
Details
- ISSN :
- 24721972
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of the Endocrine Society
- Accession number :
- edsair.doi.dedup.....8366a0413e0ecc94ec8ccc651737c4ce
- Full Text :
- https://doi.org/10.1210/jendso/bvaa191