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MIM_PhD_THESIS.pdf (4.22 MB)

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Doctoral thesis

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Published version

Publication date

2013-10-04

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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/47063

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

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Abstract

[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.

Subject

Teixit adipós, Obesitat, Resistència a la insulina, Carnitina palmitoïl-transferasa 1

Subject (English)

Adipose tissues, Obesity, Insulin resistance, Carnitine palmitoyltransferase I

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Tesis Doctorals - Departament - Bioquímica i Biologia Molecular (Farmàcia)

Citation

MALANDRINO, Maria Ida. Study of carnitine palmitoyltransferase 1A (CPT1A) in adipose tissue. Effects on obesity, inflammation and insulin resistance. [consulted: 12 of June of 2026]. Available at: https://hdl.handle.net/2445/47063

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