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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Detalles Bibliográficos
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
Descripción
Sumario:[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.