Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation

Autores
Lian, Jihong; Watts, Russell; Quiroga, Ariel Dario; Beggs, Megan R.; Alexander, R. Todd; Lehner, Richard
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Triacylglycerol accumulation in the liver is a hallmark of NAFLD. Metabolic studies have confirmed that increased hepatic de novo lipogenesis (DNL) in humans contributes to fat accumulation in the liver and to NAFLD progression. Mice deficient in carboxylesterase (Ces)1d expression are protected from high-fat diet-induced hepatic steatosis. To investigate whether loss of Ces1d can also mitigate steatosis induced by over-activated DNL, WT and Ces1d-deficient mice were fed a lipogenic high-sucrose diet (HSD). We found that Ces1d-deficient mice were protected from HSD-induced hepatic lipid accumulation. Mechanistically, Ces1d deficiency leads to activation of AMP-activated protein kinase and inhibitory phosphorylation of acetyl-CoA carboxylase. Together with our previous demonstration that Ces1d deficiency attenuated high-fat diet-induced steatosis, this study suggests that inhibition of CES1 (the human ortholog of Ces1d) might represent a novel pharmacological target for prevention and treatment of NAFLD.
Fil: Lian, Jihong. University of Alberta; Canadá
Fil: Watts, Russell. University of Alberta; Canadá
Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Beggs, Megan R.. University of Alberta; Canadá
Fil: Alexander, R. Todd. University of Alberta; Canadá
Fil: Lehner, Richard. University of Alberta; Canadá
Materia
CARBOXYLESTERASE 1D
LIPOGENESIS
LIVER
NONALCOHOLIC FATTY LIVER DISEASE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/120530
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/120530
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulationLian, JihongWatts, RussellQuiroga, Ariel DarioBeggs, Megan R.Alexander, R. ToddLehner, RichardCARBOXYLESTERASE 1DLIPOGENESISLIVERNONALCOHOLIC FATTY LIVER DISEASEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Triacylglycerol accumulation in the liver is a hallmark of NAFLD. Metabolic studies have confirmed that increased hepatic de novo lipogenesis (DNL) in humans contributes to fat accumulation in the liver and to NAFLD progression. Mice deficient in carboxylesterase (Ces)1d expression are protected from high-fat diet-induced hepatic steatosis. To investigate whether loss of Ces1d can also mitigate steatosis induced by over-activated DNL, WT and Ces1d-deficient mice were fed a lipogenic high-sucrose diet (HSD). We found that Ces1d-deficient mice were protected from HSD-induced hepatic lipid accumulation. Mechanistically, Ces1d deficiency leads to activation of AMP-activated protein kinase and inhibitory phosphorylation of acetyl-CoA carboxylase. Together with our previous demonstration that Ces1d deficiency attenuated high-fat diet-induced steatosis, this study suggests that inhibition of CES1 (the human ortholog of Ces1d) might represent a novel pharmacological target for prevention and treatment of NAFLD.Fil: Lian, Jihong. University of Alberta; CanadáFil: Watts, Russell. University of Alberta; CanadáFil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Beggs, Megan R.. University of Alberta; CanadáFil: Alexander, R. Todd. University of Alberta; CanadáFil: Lehner, Richard. University of Alberta; CanadáAmerican Society for Biochemistry and Molecular Biology2019-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/120530Lian, Jihong; Watts, Russell; Quiroga, Ariel Dario; Beggs, Megan R.; Alexander, R. Todd; et al.; Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 60; 4; 4-2019; 880-8910022-22751539-7262CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1194/jlr.M092544info:eu-repo/semantics/altIdentifier/url/https://www.jlr.org/content/60/4/880info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:03:57Zoai:ri.conicet.gov.ar:11336/120530instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:03:58.084CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation
title Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation
spellingShingle Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation
Lian, Jihong
CARBOXYLESTERASE 1D
LIPOGENESIS
LIVER
NONALCOHOLIC FATTY LIVER DISEASE
title_short Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation
title_full Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation
title_fullStr Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation
title_full_unstemmed Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation
title_sort Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation
dc.creator.none.fl_str_mv Lian, Jihong
Watts, Russell
Quiroga, Ariel Dario
Beggs, Megan R.
Alexander, R. Todd
Lehner, Richard
author Lian, Jihong
author_facet Lian, Jihong
Watts, Russell
Quiroga, Ariel Dario
Beggs, Megan R.
Alexander, R. Todd
Lehner, Richard
author_role author
author2 Watts, Russell
Quiroga, Ariel Dario
Beggs, Megan R.
Alexander, R. Todd
Lehner, Richard
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CARBOXYLESTERASE 1D
LIPOGENESIS
LIVER
NONALCOHOLIC FATTY LIVER DISEASE
topic CARBOXYLESTERASE 1D
LIPOGENESIS
LIVER
NONALCOHOLIC FATTY LIVER DISEASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Triacylglycerol accumulation in the liver is a hallmark of NAFLD. Metabolic studies have confirmed that increased hepatic de novo lipogenesis (DNL) in humans contributes to fat accumulation in the liver and to NAFLD progression. Mice deficient in carboxylesterase (Ces)1d expression are protected from high-fat diet-induced hepatic steatosis. To investigate whether loss of Ces1d can also mitigate steatosis induced by over-activated DNL, WT and Ces1d-deficient mice were fed a lipogenic high-sucrose diet (HSD). We found that Ces1d-deficient mice were protected from HSD-induced hepatic lipid accumulation. Mechanistically, Ces1d deficiency leads to activation of AMP-activated protein kinase and inhibitory phosphorylation of acetyl-CoA carboxylase. Together with our previous demonstration that Ces1d deficiency attenuated high-fat diet-induced steatosis, this study suggests that inhibition of CES1 (the human ortholog of Ces1d) might represent a novel pharmacological target for prevention and treatment of NAFLD.
Fil: Lian, Jihong. University of Alberta; Canadá
Fil: Watts, Russell. University of Alberta; Canadá
Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Beggs, Megan R.. University of Alberta; Canadá
Fil: Alexander, R. Todd. University of Alberta; Canadá
Fil: Lehner, Richard. University of Alberta; Canadá
description Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Triacylglycerol accumulation in the liver is a hallmark of NAFLD. Metabolic studies have confirmed that increased hepatic de novo lipogenesis (DNL) in humans contributes to fat accumulation in the liver and to NAFLD progression. Mice deficient in carboxylesterase (Ces)1d expression are protected from high-fat diet-induced hepatic steatosis. To investigate whether loss of Ces1d can also mitigate steatosis induced by over-activated DNL, WT and Ces1d-deficient mice were fed a lipogenic high-sucrose diet (HSD). We found that Ces1d-deficient mice were protected from HSD-induced hepatic lipid accumulation. Mechanistically, Ces1d deficiency leads to activation of AMP-activated protein kinase and inhibitory phosphorylation of acetyl-CoA carboxylase. Together with our previous demonstration that Ces1d deficiency attenuated high-fat diet-induced steatosis, this study suggests that inhibition of CES1 (the human ortholog of Ces1d) might represent a novel pharmacological target for prevention and treatment of NAFLD.
publishDate 2019
dc.date.none.fl_str_mv 2019-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/120530
Lian, Jihong; Watts, Russell; Quiroga, Ariel Dario; Beggs, Megan R.; Alexander, R. Todd; et al.; Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 60; 4; 4-2019; 880-891
0022-2275
1539-7262
CONICET Digital
CONICET
url http://hdl.handle.net/11336/120530
identifier_str_mv Lian, Jihong; Watts, Russell; Quiroga, Ariel Dario; Beggs, Megan R.; Alexander, R. Todd; et al.; Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 60; 4; 4-2019; 880-891
0022-2275
1539-7262
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1194/jlr.M092544
info:eu-repo/semantics/altIdentifier/url/https://www.jlr.org/content/60/4/880
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269829372837888
score 13.13397

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