The reverse cholesterol transport is a multistep process whereby excess cholesterol is transported by HDL from the peripheral tissues to the liver for excretion. In this study, the impact of genetic manipulation of HDL/apoA-I levels on lipid deposition in liver and kidney was investigated. Mice with extremely low plasma HDL levels, deficient for both murine apoA-I and apoE (DKO), were compared with mice characterized by elevated HDL, deficient for both apoA-I/apoE, but overexpressing human apoA-I (DKO/hA-I). Mice, both female and male, were fed a standard rodent diet until one year of age. Plasma lipids were quantified by enzymatic methods. Liver and kidney morphology was evaluated by light microscopy on frozen sections. Plasma total cholesterol concentration in DKO mice was comparable with that of wild type mice and 3-fold lower than that observed in DKO/hA-I mice. Plasma HDL-C was almost absent in DKO mice and strongly elevated in DKO/hA-I mice. The H&E-stained sections did not reveal the presence of steatosis in liver parenchyma as well as of foam cells in renal glomeruli of both genotypes. The neutral lipid-specific staining with Oil Red O showed instead interesting differences. In the hepatic parenchyma, an increased accumulation of lipids around the centrilobular vein was observed only in DKO/hA-I mice. In addition, within the glomeruli of DKO/hA-I mice, lipid accumulation was significantly higher than in DKO, both in females and males. Although DKO mice are almost completely devoid of HDL and prone to atherosclerosis development, they do not exhibit steatosis or other signs of abnormal lipid accumulation in the liver and do not develop glomerular lipidosis.

Histological assessment of lipid deposition in tissues from genetically modified mice with deficiency or overexpression of apolipoprotein A-I / E. Franchi, G. Chiesa, S. Manzini, A. Colombo, M. Busnelli. ((Intervento presentato al 75. convegno Congresso Nazionale SIAI tenutosi a Padova : 14 – 16 Settembre nel 2022.

Histological assessment of lipid deposition in tissues from genetically modified mice with deficiency or overexpression of apolipoprotein A-I

E. Franchi
;
G. Chiesa;S. Manzini;A. Colombo;M. Busnelli
2022

Abstract

The reverse cholesterol transport is a multistep process whereby excess cholesterol is transported by HDL from the peripheral tissues to the liver for excretion. In this study, the impact of genetic manipulation of HDL/apoA-I levels on lipid deposition in liver and kidney was investigated. Mice with extremely low plasma HDL levels, deficient for both murine apoA-I and apoE (DKO), were compared with mice characterized by elevated HDL, deficient for both apoA-I/apoE, but overexpressing human apoA-I (DKO/hA-I). Mice, both female and male, were fed a standard rodent diet until one year of age. Plasma lipids were quantified by enzymatic methods. Liver and kidney morphology was evaluated by light microscopy on frozen sections. Plasma total cholesterol concentration in DKO mice was comparable with that of wild type mice and 3-fold lower than that observed in DKO/hA-I mice. Plasma HDL-C was almost absent in DKO mice and strongly elevated in DKO/hA-I mice. The H&E-stained sections did not reveal the presence of steatosis in liver parenchyma as well as of foam cells in renal glomeruli of both genotypes. The neutral lipid-specific staining with Oil Red O showed instead interesting differences. In the hepatic parenchyma, an increased accumulation of lipids around the centrilobular vein was observed only in DKO/hA-I mice. In addition, within the glomeruli of DKO/hA-I mice, lipid accumulation was significantly higher than in DKO, both in females and males. Although DKO mice are almost completely devoid of HDL and prone to atherosclerosis development, they do not exhibit steatosis or other signs of abnormal lipid accumulation in the liver and do not develop glomerular lipidosis.
Settore BIO/16 - Anatomia Umana
Settore BIO/14 - Farmacologia
Histological assessment of lipid deposition in tissues from genetically modified mice with deficiency or overexpression of apolipoprotein A-I / E. Franchi, G. Chiesa, S. Manzini, A. Colombo, M. Busnelli. ((Intervento presentato al 75. convegno Congresso Nazionale SIAI tenutosi a Padova : 14 – 16 Settembre nel 2022.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/943694
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