Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?

Autores
Amati, Francesca; Dubé, John J.; Alvarez Carnero, Elvis; Edreira, Martin Miguel; Chomentowski, Peter; Coen, Paul M.; Switzer, Galen E.; Bickel, Perry E.; Stefanovic Racic, Maja; Toledo, Frederico G. S.; Goodpaster, Bret H.
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
OBJECTIVE - Chronic exercise and obesity both increase intramyocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercisetrained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS - A total of 14 normalweight, endurance-trained athletes (NWA group) and 7 normalweight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies. RESULTS - DAG content in the NWA group was approximately twofold higher than in the OBS group and ~50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/ perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin sensitivity. CONCLUSIONS - Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance.
Fil: Amati, Francesca. University of Pittsburgh; Estados Unidos. Universite de Lausanne; Suiza
Fil: Dubé, John J.. University of Pittsburgh; Estados Unidos
Fil: Alvarez Carnero, Elvis. University of Pittsburgh; Estados Unidos
Fil: Edreira, Martin Miguel. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Chomentowski, Peter. University of Pittsburgh; Estados Unidos
Fil: Coen, Paul M.. University of Pittsburgh; Estados Unidos
Fil: Switzer, Galen E.. University of Pittsburgh; Estados Unidos. Center for Health Equity Research and Promotion; Estados Unidos
Fil: Bickel, Perry E.. University of Texas Health Science Center at Houston; Estados Unidos
Fil: Stefanovic Racic, Maja. University of Pittsburgh; Estados Unidos
Fil: Toledo, Frederico G. S.. University of Pittsburgh; Estados Unidos
Fil: Goodpaster, Bret H.. University of Pittsburgh; Estados Unidos
Materia
Triglycerides
Diacylglycerols
Ceramides
Insulin Resistance
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:11336/79425

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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?Amati, FrancescaDubé, John J.Alvarez Carnero, ElvisEdreira, Martin MiguelChomentowski, PeterCoen, Paul M.Switzer, Galen E.Bickel, Perry E.Stefanovic Racic, MajaToledo, Frederico G. S.Goodpaster, Bret H.TriglyceridesDiacylglycerolsCeramidesInsulin Resistancehttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3OBJECTIVE - Chronic exercise and obesity both increase intramyocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercisetrained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS - A total of 14 normalweight, endurance-trained athletes (NWA group) and 7 normalweight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies. RESULTS - DAG content in the NWA group was approximately twofold higher than in the OBS group and ~50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/ perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin sensitivity. CONCLUSIONS - Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance.Fil: Amati, Francesca. University of Pittsburgh; Estados Unidos. Universite de Lausanne; SuizaFil: Dubé, John J.. University of Pittsburgh; Estados UnidosFil: Alvarez Carnero, Elvis. University of Pittsburgh; Estados UnidosFil: Edreira, Martin Miguel. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Chomentowski, Peter. University of Pittsburgh; Estados UnidosFil: Coen, Paul M.. University of Pittsburgh; Estados UnidosFil: Switzer, Galen E.. University of Pittsburgh; Estados Unidos. Center for Health Equity Research and Promotion; Estados UnidosFil: Bickel, Perry E.. University of Texas Health Science Center at Houston; Estados UnidosFil: Stefanovic Racic, Maja. University of Pittsburgh; Estados UnidosFil: Toledo, Frederico G. S.. University of Pittsburgh; Estados UnidosFil: Goodpaster, Bret H.. University of Pittsburgh; Estados UnidosAmerican Diabetes Association2011-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79425Amati, Francesca; Dubé, John J.; Alvarez Carnero, Elvis; Edreira, Martin Miguel; Chomentowski, Peter; et al.; Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?; American Diabetes Association; Diabetes; 60; 10; 10-2011; 2588-25970012-1797CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21873552/info:eu-repo/semantics/altIdentifier/doi/10.2337/db10-1221info:eu-repo/semantics/altIdentifier/url/https://diabetes.diabetesjournals.org/content/60/10/2588info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:40:43Zoai:ri.conicet.gov.ar:11336/79425instacron: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:34982025-09-29 10:40:43.445CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?
title Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?
spellingShingle Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?
Amati, Francesca
Triglycerides
Diacylglycerols
Ceramides
Insulin Resistance
title_short Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?
title_full Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?
title_fullStr Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?
title_full_unstemmed Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?
title_sort Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?
dc.creator.none.fl_str_mv Amati, Francesca
Dubé, John J.
Alvarez Carnero, Elvis
Edreira, Martin Miguel
Chomentowski, Peter
Coen, Paul M.
Switzer, Galen E.
Bickel, Perry E.
Stefanovic Racic, Maja
Toledo, Frederico G. S.
Goodpaster, Bret H.
author Amati, Francesca
author_facet Amati, Francesca
Dubé, John J.
Alvarez Carnero, Elvis
Edreira, Martin Miguel
Chomentowski, Peter
Coen, Paul M.
Switzer, Galen E.
Bickel, Perry E.
Stefanovic Racic, Maja
Toledo, Frederico G. S.
Goodpaster, Bret H.
author_role author
author2 Dubé, John J.
Alvarez Carnero, Elvis
Edreira, Martin Miguel
Chomentowski, Peter
Coen, Paul M.
Switzer, Galen E.
Bickel, Perry E.
Stefanovic Racic, Maja
Toledo, Frederico G. S.
Goodpaster, Bret H.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Triglycerides
Diacylglycerols
Ceramides
Insulin Resistance
topic Triglycerides
Diacylglycerols
Ceramides
Insulin Resistance
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv OBJECTIVE - Chronic exercise and obesity both increase intramyocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercisetrained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS - A total of 14 normalweight, endurance-trained athletes (NWA group) and 7 normalweight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies. RESULTS - DAG content in the NWA group was approximately twofold higher than in the OBS group and ~50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/ perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin sensitivity. CONCLUSIONS - Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance.
Fil: Amati, Francesca. University of Pittsburgh; Estados Unidos. Universite de Lausanne; Suiza
Fil: Dubé, John J.. University of Pittsburgh; Estados Unidos
Fil: Alvarez Carnero, Elvis. University of Pittsburgh; Estados Unidos
Fil: Edreira, Martin Miguel. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Chomentowski, Peter. University of Pittsburgh; Estados Unidos
Fil: Coen, Paul M.. University of Pittsburgh; Estados Unidos
Fil: Switzer, Galen E.. University of Pittsburgh; Estados Unidos. Center for Health Equity Research and Promotion; Estados Unidos
Fil: Bickel, Perry E.. University of Texas Health Science Center at Houston; Estados Unidos
Fil: Stefanovic Racic, Maja. University of Pittsburgh; Estados Unidos
Fil: Toledo, Frederico G. S.. University of Pittsburgh; Estados Unidos
Fil: Goodpaster, Bret H.. University of Pittsburgh; Estados Unidos
description OBJECTIVE - Chronic exercise and obesity both increase intramyocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercisetrained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS - A total of 14 normalweight, endurance-trained athletes (NWA group) and 7 normalweight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies. RESULTS - DAG content in the NWA group was approximately twofold higher than in the OBS group and ~50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/ perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin sensitivity. CONCLUSIONS - Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance.
publishDate 2011
dc.date.none.fl_str_mv 2011-10
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/11336/79425
Amati, Francesca; Dubé, John J.; Alvarez Carnero, Elvis; Edreira, Martin Miguel; Chomentowski, Peter; et al.; Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?; American Diabetes Association; Diabetes; 60; 10; 10-2011; 2588-2597
0012-1797
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79425
identifier_str_mv Amati, Francesca; Dubé, John J.; Alvarez Carnero, Elvis; Edreira, Martin Miguel; Chomentowski, Peter; et al.; Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?; American Diabetes Association; Diabetes; 60; 10; 10-2011; 2588-2597
0012-1797
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21873552/
info:eu-repo/semantics/altIdentifier/doi/10.2337/db10-1221
info:eu-repo/semantics/altIdentifier/url/https://diabetes.diabetesjournals.org/content/60/10/2588
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 Diabetes Association
publisher.none.fl_str_mv American Diabetes Association
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
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