Innovative strategy to combat obesity

Some scientists have designed a strategy to combat obesity and diabetes through ex vivo gene therapy that consists of implanting cells that have been manipulated and transformed in order to treat one of these diseases. For now, the method has only been tested in mice.

This is the first time that he has applied the ex vivo gene therapy technique to generate and implant cells capable of expressing the CPT1AM protein, an enzyme that plays a decisive role in many metabolic diseases such as obesity.

The work is the work of specialists from the University of Barcelona (UB) and the Network Biomedical Research Center for Physiopathology of Obesity and Nutrition (CIBEROBN), in Spain. The team includes M. Carmen Soler-Vázquez, from the Institute of Biomedicine of the University of Barcelona (IBUB), and Laura Herrero, from the Faculty of Pharmacy and Food Sciences of the UB, IBUB, and CIBEROBN.

Cell therapy describes the process of introducing new cells into a tissue in order to fight this disease. Currently, cell therapies are focused on addressing hereditary diseases —with or without the help of gene therapy— or degenerative diseases.

“In this new therapy, animal models have been implanted subcutaneously with stem cells derived from adipose tissue and differentiated into adipocytes so that they can express an active form of the CPT1AM protein, an enzyme located in mitochondria that is key in lipid oxidation and is related to metabolic diseases”, says Laura Herrero, member of the Department of Biochemistry and Physiology of the UB.

«As a result, in obese mice it has been possible to reduce weight, fatty liver condition (hepatic steatosis) and cholesterol and glucose levels. In conclusion, implantation of adipocytes expressing the mitochondrial enzyme CPT1AM helps to reduce obesity and glucose intolerance in mice.”

As the cell transformation process takes place outside the body of the organism, this type of therapy is much easier to carry out and allows greater control of the altered cells.

Professor Laura Herrero. (Photo: UB / IBUB).

Obesity and cell therapy

Obesity and associated metabolic disorders represent a health and social problem throughout the world, which is why new therapeutic approaches must be urgently promoted. Adipose tissue has a key role in regulating energy balance, and mesenchymal stem cells have gained interest in cell therapy.

“Specifically, carnitine palmitoyltransferase 1A (CPT1A) is the enzyme that controls the mitochondrial oxidation of fatty acids. Our goal was to generate adipocytes that could express a constitutively active form of CPT1A – CPT1AM – capable of burning excess fat and improving the obese metabolic phenotype of mice after implantation.”

The results of the new research work support the future clinical use of this ex vivo gene therapy approach as a new strategy to reduce obesity and cholesterol rates in the population.

This work, of a preclinical nature, could open the doors to future therapeutic strategies to address the treatment of obesity, which today represents a global health problem.

“To use the therapy in humans, we need to optimize several processes such as the quality and viability of stem cells from adipose tissue isolated from people with obesity, the percentage of infection with lentiviruses, and the number of cells used for transplantation,” concludes the researcher. Laura Herrero.

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The study is titled “Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice.” And it has been published in the academic journal Metabolic Engineering. (Source: UB / IBUB)