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CPT1AM overexpression in BAT from HFD-treated mice prevents the induction of obesity and associated diabetes
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[eng] Obesity and its associated metabolic diseases are currently a priority research topic. The increase in global prevalence at different ages is having a huge economic and health impact. Genetic and environmental factors play a crucial role in the development of obesity, and diet is one of the main factors that directly contributes to the genic obese phenotype. Scientific evidence has shown that increased fat intake is associated with increased body weight that triggers obesity. Rodent animal models have been extremely useful in the study of obesity, as weight gain can be easily induced by a high-fat diet.
On the other hand, thermogenesis is a process that our body uses to produce heat. Studies show that the body uses a variety of mechanisms to produce this effect, demonstrating that brown adipose tissue (BAT) is one of the main effector organs. In general, adipose tissue is the organ where energy is stored in the form of fat (triacylglycerols), while BAT, in particular, owes its name to the color that characterizes the presence of a large number of mitochondria, which have a high concentration of uncoupling proteins (UCP}, in addition to a good number of a and beta-adrenergic receptors and high vascularization. BAT is located in specific areas of the body such as the cervical area of the neck, armpits, associated with the ribs, around the heart and kidneys, showing a greater distribution in fetuses and newborns compared to adults.
Understanding the activity of adipose tissue is important because of the involvement of this organ in the pathophysiology of obesity. Mitochondria burn fuels such as fatty acids and glucose into useful energy, consuming oxygen in the process. In addition, BAT has a high concentration of the protein UCP1 (uncoupling protein 1). This protein bypasses the respiratory chain, so instead of generating useful energy, it dissipates energy as heat. This function, known as non-shivering thermogenesis, is crucial in infants to maintain body temperature. BAT has emerged as an important regulator of energy expenditure in obesity by controlling thermogenesis. Carnitine palmitoyltransferase 1A (CPT1A), a key enzyme in fatty acid oxidation (FAO), has been implicated in the control of energy homeostasis. However, the specific role of CPT1A in modulating BAT metabolism to control food intake and obesity is still highly unknown.
The aim of this research work was to find new approaches to reduce obesity by activating CPT1A, and thus FAO, in BAT.
For peripheral activation of FAO in BAT, the mutated and permanently active form (CPT1AM) was expressed. This was done in mice in vivo using adeno-associated (AAV) vectors. As a result, activation of CPT1A in BAT activated thermogenesis and reduced weight gain, identifying new strategy for potential therapy against obesity and its associated metabolic diseases, such as diabetes.
In addition, our results showed that expression of CPT1AM in BAT increased lipolysis FAO and thermogenesis in BAT. The increase FAO in BAT prevented the increase in the content of triglycerides, cholesterol and insulin in the blood, and the expression of markers of obesity and inflammation in the tissues, caused by HFD. Our results show that FAO is critical in supplying fuel for BAT-generated thermogenesis, which may be a good strategy to increase energy expenditure through thermogenesis and thus avoid obesity and its associated diseases resulting from HFD.
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BASTÍAS PÉREZ, Marianela pía. CPT1AM overexpression in BAT from HFD-treated mice prevents the induction of obesity and associated diabetes. [consulta: 29 de novembre de 2025]. [Disponible a: https://hdl.handle.net/2445/192726]