Obesity is a risk factor for metabolic pathologies such as insulin resistance, T2D, dyslipidemia, cardiovascular disease, and cancer. The pathophysiology of obesity-induced metabolic complications includes chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, impaired angiogenesis, hypoxia, and cell death.
A research team from the University of Barcelona and the CIBERobn has developed a way to fight obesity and diabetes in mice using ex vivo gene therapy, which involves implanting cells that have been modified and transformed to cure a condition.
This is the first study to use ex vivo gene therapy to create and implant cells expressing the CPT1AM protein. This enzyme is important in several metabolic illnesses, such as obesity.
Laura Herrero, a member of the UB Department of Biochemistry and Physiology, said, “In this new therapy, animal models have been implanted subcutaneously stem cells derived from adipose tissue, differentiated into adipocytes so that they can express an active form of the CPT1AM protein, an enzyme located in the mitochondria that are key in lipid oxidation and are related to metabolic diseases.”
In obese mice, implantation of adipocytes expressing the mitochondrial enzyme CPT1AM reduced weight, fatty liver (hepatic steatosis), cholesterol, and glucose levels.
Cell therapy is the process of inserting new cells into a tissue to fight illness. Cell therapies are now being developed to treat genetic disorders, both with and without the assistance of gene therapy, as well as degenerative diseases.
This type of therapy is less difficult to administer and allows for greater control over the changed cells. Adipose tissue regulates energy balance, and adipose-derived mesenchymal stem cells are being studied for cell therapy. The goal was to create adipocytes that expressed a constitutively active version of CPT1A, capable of burning extra fat and improving mice’s obese metabolic profile after implantation.
Obesity and related metabolic disorders are a global health and social challenge which necessitates the development of novel therapeutic techniques. Adipose tissue regulates energy balance, and adipose-derived mesenchymal stem cells are being studied for cell therapy.
This preclinical work may open the way for future medicinal techniques to fight obesity, which is currently a global health issue.
Researcher Laura Herrero concludes, “To approximate 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 lentivirus, and the number of cells used for transplantation.”
The results of this latest study indicate the potential practical application of this ex vivo gene therapy technique as an innovative approach to lowering obesity and cholesterol levels in the general population.
- Soler-Vázquez, M. C., Romero,etal. Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice. Metabolic Engineering. DOI: 10.1016/j.ymben.2023.04.010