Study of carnitine palmitoyltransferase 1A (CPT1A) in adipose tissue. Effects on obesity, inflammation and insulin resistance

[eng] Current lifestyle with high-energy diets and little exercise is triggering an alarming growth in obesity. Excess of adiposity is leading to severe increase in associated pathologies, such as insulin resistance, type 2 diabetes (T2DM), atherosclerosis, cancer, arthritis, asthma, and hypertensio...

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Autor: Malandrino, Maria Ida
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/47063
Acceso en línea:https://hdl.handle.net/2445/47063
http://hdl.handle.net/10803/123966
Access Level:acceso abierto
Palabra clave:Teixit adipós
Obesitat
Resistència a la insulina
Carnitina palmitoïl-transferasa 1
Adipose tissues
Obesity
Insulin resistance
Carnitine palmitoyltransferase I
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spelling Study of carnitine palmitoyltransferase 1A (CPT1A) in adipose tissue. Effects on obesity, inflammation and insulin resistanceMalandrino, Maria IdaTeixit adipósObesitatResistència a la insulinaCarnitina palmitoïl-transferasa 1Adipose tissuesObesityInsulin resistanceCarnitine palmitoyltransferase I[eng] Current lifestyle with high-energy diets and little exercise is triggering an alarming growth in obesity. Excess of adiposity is leading to severe increase in associated pathologies, such as insulin resistance, type 2 diabetes (T2DM), atherosclerosis, cancer, arthritis, asthma, and hypertension. This, together with the lack of efficient anticobesity drugs, is the driving force behind much research. Obesity is associated with adipocyte dysfunction, macrophage infiltration, inflammation and decreased fatty acid oxidation (FAO) levels. Recent results suggest that enhancing cellular energy expenditure may be an attractive alternative therapy. In this study, we propose that an increase in adipocytes and macrophages FAO rate could protect from obesity and insulin resistance by a decrease in the lipid content and inflammatory levels. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rateclimiting enzyme in mitochondrial FAO) in 3T3cL1 CAR-Delta1 adipocytes and RAW 264.7 macrophages by adenovirus infection. Visceral and subcutaneous adipose tissue (VAT and SAT, respectively) samples from lean, overweight, obese and diabetic patients were studied. CPT1AM-expressing adipocytes and macrophages had increased FAO and showed a reduction in palmitatecinduced increase in triglyceride content, inflammation, endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) levels compared to GFP control cells. CPT1AM expression was able to restore palmitate-induced impairment in adipocyte insulin signaling.Universitat de BarcelonaHerrero Rodríguez, LauraGarcía Hegardt, FaustoUniversitat de Barcelona. Departament de Bioquímica i Biologia Molecular (Farmàcia)2013info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/47063http://hdl.handle.net/10803/123966Tesis Doctorals - Departament - Bioquímica i Biologia Molecular (Farmàcia)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Malandrino,, 2013info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/470632026-05-27T06:46:51Z
dc.title.none.fl_str_mv Study of carnitine palmitoyltransferase 1A (CPT1A) in adipose tissue. Effects on obesity, inflammation and insulin resistance
title Study of carnitine palmitoyltransferase 1A (CPT1A) in adipose tissue. Effects on obesity, inflammation and insulin resistance
spellingShingle Study of carnitine palmitoyltransferase 1A (CPT1A) in adipose tissue. Effects on obesity, inflammation and insulin resistance
Malandrino, Maria Ida
Teixit adipós
Obesitat
Resistència a la insulina
Carnitina palmitoïl-transferasa 1
Adipose tissues
Obesity
Insulin resistance
Carnitine palmitoyltransferase I
title_short Study of carnitine palmitoyltransferase 1A (CPT1A) in adipose tissue. Effects on obesity, inflammation and insulin resistance
title_full Study of carnitine palmitoyltransferase 1A (CPT1A) in adipose tissue. Effects on obesity, inflammation and insulin resistance
title_fullStr Study of carnitine palmitoyltransferase 1A (CPT1A) in adipose tissue. Effects on obesity, inflammation and insulin resistance
title_full_unstemmed Study of carnitine palmitoyltransferase 1A (CPT1A) in adipose tissue. Effects on obesity, inflammation and insulin resistance
title_sort Study of carnitine palmitoyltransferase 1A (CPT1A) in adipose tissue. Effects on obesity, inflammation and insulin resistance
dc.creator.none.fl_str_mv Malandrino, Maria Ida
author Malandrino, Maria Ida
author_facet Malandrino, Maria Ida
author_role author
dc.contributor.none.fl_str_mv Herrero Rodríguez, Laura
García Hegardt, Fausto
Universitat de Barcelona. Departament de Bioquímica i Biologia Molecular (Farmàcia)
dc.subject.none.fl_str_mv Teixit adipós
Obesitat
Resistència a la insulina
Carnitina palmitoïl-transferasa 1
Adipose tissues
Obesity
Insulin resistance
Carnitine palmitoyltransferase I
topic Teixit adipós
Obesitat
Resistència a la insulina
Carnitina palmitoïl-transferasa 1
Adipose tissues
Obesity
Insulin resistance
Carnitine palmitoyltransferase I
description [eng] Current lifestyle with high-energy diets and little exercise is triggering an alarming growth in obesity. Excess of adiposity is leading to severe increase in associated pathologies, such as insulin resistance, type 2 diabetes (T2DM), atherosclerosis, cancer, arthritis, asthma, and hypertension. This, together with the lack of efficient anticobesity drugs, is the driving force behind much research. Obesity is associated with adipocyte dysfunction, macrophage infiltration, inflammation and decreased fatty acid oxidation (FAO) levels. Recent results suggest that enhancing cellular energy expenditure may be an attractive alternative therapy. In this study, we propose that an increase in adipocytes and macrophages FAO rate could protect from obesity and insulin resistance by a decrease in the lipid content and inflammatory levels. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rateclimiting enzyme in mitochondrial FAO) in 3T3cL1 CAR-Delta1 adipocytes and RAW 264.7 macrophages by adenovirus infection. Visceral and subcutaneous adipose tissue (VAT and SAT, respectively) samples from lean, overweight, obese and diabetic patients were studied. CPT1AM-expressing adipocytes and macrophages had increased FAO and showed a reduction in palmitatecinduced increase in triglyceride content, inflammation, endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) levels compared to GFP control cells. CPT1AM expression was able to restore palmitate-induced impairment in adipocyte insulin signaling.
publishDate 2013
dc.date.none.fl_str_mv 2013
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/47063
http://hdl.handle.net/10803/123966
url https://hdl.handle.net/2445/47063
http://hdl.handle.net/10803/123966
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv (c) Malandrino,, 2013
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Malandrino,, 2013
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Departament - Bioquímica i Biologia Molecular (Farmàcia)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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