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| Home > Articles > Published articles > Human ApoA-I overexpression enhances macrophage-specific reverse cholesterol transport but fails to prevent inherited diabesity in mice |
| Home > Articles > Published articles > Human ApoA-I overexpression enhances macrophage-specific reverse cholesterol transport but fails to prevent inherited diabesity in mice |
(Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Institut d'Investigació Biomèdica Sant Pau) (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Institut d'Investigació Biomèdica Sant Pau) (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques) (Minerva Foundation Institute for Medical Research) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
| Date: | 2019 |
| Abstract: | Human apolipoprotein A-I (hApoA-I) overexpression improves high-density lipoprotein (HDL) function and the metabolic complications of obesity. We used a mouse model of diabesity, the db/db mouse, to examine the effects of hApoA-I on the two main functional properties of HDL, i. e. , macrophage-specific reverse cholesterol transport (m-RCT) in vivo and the antioxidant potential, as well as the phenotypic features of obesity. HApoA-I transgenic (hA-I) mice were bred with nonobese control (db/+) mice to generate hApoA-I-overexpressing db/+ offspring, which were subsequently bred to obtain hA-I-db/db mice. Overexpression of hApoA-I significantly increased weight gain and the incidence of fatty liver in db/db mice. Weight gain was mainly explained by the increased caloric intake of hA-I-db/db mice (>1. 2-fold). Overexpression of hApoA-I also produced a mixed type of dyslipidemia in db/db mice. Despite these deleterious effects, the overexpression of hApoA-I partially restored m-RCT in db/db mice to levels similar to nonobese control mice. Moreover, HDL from hA-I-db/db mice also enhanced the protection against low-density lipoprotein (LDL) oxidation compared with HDL from db/db mice. In conclusion, overexpression of hApoA-I in db/db mice enhanced two main anti-atherogenic HDL properties while exacerbating weight gain and the fatty liver phenotype. These adverse metabolic side-effects were also observed in obese mice subjected to long-term HDL-based therapies in independent studies and might raise concerns regarding the use of hApoA-I-mediated therapy in obese humans. |
| Grants: | Instituto de Salud Carlos III CP13/00070 Instituto de Salud Carlos III PI17-00232 Instituto de Salud Carlos III PI12-0226 Instituto de Salud Carlos III PI11/01076 Instituto de Salud Carlos III PI17-01362 Instituto de Salud Carlos III PI16-00139 Instituto de Salud Carlos III PI16-00471 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | HDL functions ; Reverse cholesterol transport ; Metabolic syndrome ; Obesity ; Hepatic steatosis |
| Published in: | International journal of molecular sciences, Vol. 20, Issue 3 (February 2019) , art. 655, ISSN 1422-0067 |
