A research group from the University of Barcelona and the Physiopathology of Obesity and Nutrition Networking Biomedical Research Centre (CIBERobn) (Spain) has developed a strategy to fight obesity and diabetes in mice via ex vivo gene therapy that involves implanting cells that have been modified to treat the disease. The study was published in the journal Metabolic Engineering. Adipose tissue plays a key role in the regulation of energy balance and for the first time, ex vivo gene therapy has been used in this study to create and implant cells that produce the CPT1AM protein, an enzyme for mitochondrial fatty acid oxidation that is crucial in several metabolic diseases like obesity. In this new therapeutic approach, the researchers implanted subcutaneously in mouse models fed a high-fat diet (HFD) mature adipocytes generated from adipose tissue-derived mesenchymal stem cells (AT-MSCs), subjected to a lentivirus-mediated expression of a constitutively active form of CPT1AM protein. This constitutively active CPT1A form (CPT1AM) could improve the obese phenotype in mice after their implantation as CPT1AM-implanted obese mice showed lower body weight, fatty liver (hepatic steatosis), serum insulin, glucose, and cholesterol levels.
These findings suggest the clinical application of this ex vivo gene therapy in the future to treat obesity, which is currently a major worldwide health issue. This kind of therapy is simpler to administer and gives more control over the transformed cells because the cell transformation process occurs outside the body of the organism.
Reference: Soler-Vázquez MC, Romero M del M, Todorcevic M, et al. Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice. Metabolic Engineering. 2023;77:256-272. doi: 10.1016/j.ymben.2023.04.010
Image source: Graphical abstract of the study described above Carmen Soler-Vázquez et al., 2023
