Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response

ACTIS DATO, VIRGINIA; BENITEZ-AMARO, ALEYDA; GARCIA, EDUARDO; CLAUDI, LENE; LHOËST, MARIA TERESA LACHICA; IBORRA, ANTONI; ESCOLA-GIL, JOAN CARLES; GUERRA, JOSE MARIA; SAMOUILLAN, VALERIE; ENRICH, CARLOS; CHIABRANDO, GUSTAVO; LLORENTE-CORTÉS, VICENTA

BIOMEDICINE & PHARMACOTHERAPY = BIOMEDECINE & PHARMACOTHERAPIE.

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Año: 2022 vol. 152

0753-3322

ackground: Antibodies against the P3 sequence (Gly1127-Cys1140) of LRP1 (anti-P3 Abs) specifically block cholesteryl ester (CE) accumulation in vascular cells. LRP1 is a key regulator of insulin receptor (InsR) trafficking in different cell types. The link between CE accumulation and the insulin response are largely unknown. Here, the effects of P3 peptide immunization on the alterations induced by a high-fat diet (HFD) in cardiac insulin response were evaluated. Methods: Irrelevant (IrP)- or P3 peptide-immunized rabbits were randomized into groups fed either HFD or normal chow. Cardiac lipid content was characterized by thin-layer chromatography, confocal microscopy, and electron microscopy. LRP1, InsR and glucose transporter type 4 (GLUT4) levels were determined in membranes and total lysates from rabbit heart. The interaction between InsR and LRP1 was analyzed by immunoprecipitation and confocal microscopy. Insulin signaling activity and glucose uptake were evaluated in HL-1 cells