Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation.

Circulating lipopolysaccharide-binding protein (LBP) is increased in individuals with liver steatosis. We aimed to evaluate the possible impact of liver LBP downregulation using lipid nanoparticle-containing chemically modified LBP small interfering RNA (siRNA) (LNP-Lbp UNA-siRNA) on the development...

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Autores: Latorre J, Díaz-Trelles R, Comas F, Gavaldà-Navarro A, Milbank E, Dragano N, Morón-Ros S, Mukthavaram R, Ortega F, Castells-Nobau A, Oliveras-Cañellas N, Ricart W, Karmali PP, Tachikawa K, Chivukula P, Villarroya F, López M, Giralt M, Fernández-Real JM, Moreno-Navarrete JM
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p22107
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=22107
https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(22)00199-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2162253122001998%3Fshowall%3Dtrue
Access Level:acceso abierto
Palabra clave:LPS-binding protein
MT: oligonucleotides: therapies and applications
fatty liver
lipid nanoparticles
obesity
siRNAs
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spelling Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation.Latorre JDíaz-Trelles RComas FGavaldà-Navarro AMilbank EDragano NMorón-Ros SMukthavaram ROrtega FCastells-Nobau AOliveras-Cañellas NRicart WKarmali PPTachikawa KChivukula PVillarroya FLópez MGiralt MFernández-Real JMMoreno-Navarrete JMLPS-binding proteinMT: oligonucleotides: therapies and applicationsfatty liverlipid nanoparticlesobesitysiRNAsCirculating lipopolysaccharide-binding protein (LBP) is increased in individuals with liver steatosis. We aimed to evaluate the possible impact of liver LBP downregulation using lipid nanoparticle-containing chemically modified LBP small interfering RNA (siRNA) (LNP-Lbp UNA-siRNA) on the development of fatty liver. Weekly LNP-Lbp UNA-siRNA was administered to mice fed a standard chow diet, a high-fat and high-sucrose diet, and a methionine- and choline-deficient diet (MCD). In mice fed a high-fat and high-sucrose diet, which displayed induced liver lipogenesis, LBP downregulation led to reduced liver lipid accumulation, lipogenesis (mainly stearoyl-coenzyme A desaturase 1 [Scd1]) and lipid peroxidation-associated oxidative stress markers. LNP-Lbp UNA-siRNA also resulted in significantly decreased blood glucose levels during an insulin tolerance test. In mice fed a standard chow diet or an MCD, in which liver lipogenesis was not induced or was inhibited (especially Scd1 mRNA), liver LBP downregulation did not impact on liver steatosis. The link between hepatocyte LBP and lipogenesis was further confirmed in palmitate-treated Hepa1-6 cells, in primary human hepatocytes, and in subjects with morbid obesity. Altogether, these data indicate that siRNA against liver Lbp mRNA constitutes a potential target therapy for obesity-associated fatty liver through the modulation of hepatic Scd1.CELL PRESS2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=22107https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(22)00199-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2162253122001998%3Fshowall%3DtrueMOLECULAR THERAPY NUCLEIC ACIDSISSN: 21622531reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p221072026-05-27T12:37:41Z
dc.title.none.fl_str_mv Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation.
title Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation.
spellingShingle Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation.
Latorre J
LPS-binding protein
MT: oligonucleotides: therapies and applications
fatty liver
lipid nanoparticles
obesity
siRNAs
title_short Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation.
title_full Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation.
title_fullStr Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation.
title_full_unstemmed Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation.
title_sort Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation.
dc.creator.none.fl_str_mv Latorre J
Díaz-Trelles R
Comas F
Gavaldà-Navarro A
Milbank E
Dragano N
Morón-Ros S
Mukthavaram R
Ortega F
Castells-Nobau A
Oliveras-Cañellas N
Ricart W
Karmali PP
Tachikawa K
Chivukula P
Villarroya F
López M
Giralt M
Fernández-Real JM
Moreno-Navarrete JM
author Latorre J
author_facet Latorre J
Díaz-Trelles R
Comas F
Gavaldà-Navarro A
Milbank E
Dragano N
Morón-Ros S
Mukthavaram R
Ortega F
Castells-Nobau A
Oliveras-Cañellas N
Ricart W
Karmali PP
Tachikawa K
Chivukula P
Villarroya F
López M
Giralt M
Fernández-Real JM
Moreno-Navarrete JM
author_role author
author2 Díaz-Trelles R
Comas F
Gavaldà-Navarro A
Milbank E
Dragano N
Morón-Ros S
Mukthavaram R
Ortega F
Castells-Nobau A
Oliveras-Cañellas N
Ricart W
Karmali PP
Tachikawa K
Chivukula P
Villarroya F
López M
Giralt M
Fernández-Real JM
Moreno-Navarrete JM
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv LPS-binding protein
MT: oligonucleotides: therapies and applications
fatty liver
lipid nanoparticles
obesity
siRNAs
topic LPS-binding protein
MT: oligonucleotides: therapies and applications
fatty liver
lipid nanoparticles
obesity
siRNAs
description Circulating lipopolysaccharide-binding protein (LBP) is increased in individuals with liver steatosis. We aimed to evaluate the possible impact of liver LBP downregulation using lipid nanoparticle-containing chemically modified LBP small interfering RNA (siRNA) (LNP-Lbp UNA-siRNA) on the development of fatty liver. Weekly LNP-Lbp UNA-siRNA was administered to mice fed a standard chow diet, a high-fat and high-sucrose diet, and a methionine- and choline-deficient diet (MCD). In mice fed a high-fat and high-sucrose diet, which displayed induced liver lipogenesis, LBP downregulation led to reduced liver lipid accumulation, lipogenesis (mainly stearoyl-coenzyme A desaturase 1 [Scd1]) and lipid peroxidation-associated oxidative stress markers. LNP-Lbp UNA-siRNA also resulted in significantly decreased blood glucose levels during an insulin tolerance test. In mice fed a standard chow diet or an MCD, in which liver lipogenesis was not induced or was inhibited (especially Scd1 mRNA), liver LBP downregulation did not impact on liver steatosis. The link between hepatocyte LBP and lipogenesis was further confirmed in palmitate-treated Hepa1-6 cells, in primary human hepatocytes, and in subjects with morbid obesity. Altogether, these data indicate that siRNA against liver Lbp mRNA constitutes a potential target therapy for obesity-associated fatty liver through the modulation of hepatic Scd1.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=22107
https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(22)00199-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2162253122001998%3Fshowall%3Dtrue
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=22107
https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(22)00199-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2162253122001998%3Fshowall%3Dtrue
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv CELL PRESS
publisher.none.fl_str_mv CELL PRESS
dc.source.none.fl_str_mv MOLECULAR THERAPY NUCLEIC ACIDS
ISSN: 21622531
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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