Newswise — A research group from the University of Barcelona and the CIBERobn has devised a plan to combat obesity and diabetes in mice using ex vivo gene therapy. The method involves introducing modified cells to treat the condition. This study marks the initial attempt to utilize ex vivo gene therapy to create and implant cells that produce the CPT1AM protein. This enzyme holds significant importance in various metabolic disorders like obesity.
The research, featured in the Metabolic Engineering journal, is spearheaded by Professor Laura Herrero. She is affiliated with the Faculty of Pharmacy and Food Sciences and the Institute of Biomedicine at the University of Barcelona (IBUB), as well as the Physiopathology of Obesity and Nutrition Networking Biomedical Research Centre (CIBERobn).
Cell therapy refers to the procedure of introducing fresh cells into a tissue to combat a disease. Presently, cell therapies primarily target hereditary diseases, both with and without the assistance of gene therapy, as well as degenerative diseases.
Laura Herrero, a member of the UB Department of Biochemistry and Physiology, explains that in this novel therapy, stem cells derived from adipose tissue have been subcutaneously implanted in animal models. These cells have been differentiated into adipocytes to enable the expression of an active variant of the CPT1AM protein. This particular enzyme is situated within the mitochondria and plays a crucial role in lipid oxidation, while also being associated with metabolic disorders.
The outcomes of this study indicate that in obese mice, notable reductions have been achieved in terms of weight, hepatic steatosis (fatty liver), cholesterol, and glucose levels. Consequently, the implantation of adipocytes that express the mitochondrial enzyme CPT1AM has proven effective in diminishing obesity and improving glucose intolerance in mice.
Since the process of cell transformation occurs outside the organism's body, this form of therapy becomes considerably more manageable and grants enhanced control over the modified cells.
Obesity and cell therapy
Obesity and the related metabolic disorders pose significant global health and societal challenges, necessitating the development of new therapeutic strategies. Adipose tissue, with its crucial role in energy regulation, has emerged as a focal point for research. Adipose-derived mesenchymal stem cells, possessing the capacity for self-renewal, have garnered attention in the field of cell therapy. These cells hold promise for potential therapeutic interventions.
The primary objective of the study was to produce adipocytes capable of expressing a constitutively active variant of the enzyme carnitine palmitoyltransferase 1A (CPT1A), known as CPT1AM. CPT1A is responsible for regulating fatty acid oxidation within the mitochondria. By implanting these modified adipocytes, the researchers aimed to enhance fat-burning capabilities and ameliorate the metabolic phenotype associated with obesity in mice.
The findings from this recent study provide support for the potential clinical application of ex vivo gene therapy as a novel approach to combat obesity and reduce cholesterol levels in the general population. This preclinical investigation may serve as a stepping stone towards future therapeutic strategies aimed at addressing the global health issue of obesity.
Researcher Laura Herrero concludes that in order to adapt this therapy for human use, several processes need to be optimized. These include enhancing the quality and viability of stem cells derived from adipose tissue obtained from individuals with obesity, optimizing the infection rate with lentivirus, and determining the optimal number of cells for transplantation. These optimizations are crucial steps towards advancing this therapy for potential use in humans.
Reference article:
Soler-Vázquez, M. C.; Romero, M.; Todorcevic, M.; Delgado, K.; Calatayud, C.; Benítez-Amaro, A.; La Chica Lhoëst, M.T.; Mera, P.; Zagmutt, S.; Bastías-Pérez, M.; Ibeas, K.; Casals, N.; Escolà-Gil, J.C.; Llorente-Cortés, V.; Consiglio, A.; Serra, D.; Herrero, L. “Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice”. Metabolic Engineering, April 2023. doi.org/10.1016/j.ymben.2023.04.010
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