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Encapsulation Thermogenic Preadipocytes for Transplantation into Adipose Tissue Depots
Published on: June 2, 2015
Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice
M Carmen Soler-Vázquez1, María Del Mar Romero2, Marijana Todorcevic1
1Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Institute of Biomedicine of the University of Barcelona (IBUB), Universitat de Barcelona (UB), E-08028, Barcelona, Spain.
Abstract:
Obesity and its associated metabolic comorbidities are a rising global health and social issue, with novel therapeutic approaches urgently needed. Adipose tissue plays a key role in the regulation of energy balance and adipose tissue-derived mesenchymal stem cells (AT-MSCs) have gained great interest in cell therapy. Carnitine palmitoyltransferase 1A (CPT1A) is the gatekeeper enzyme for mitochondrial fatty acid oxidation. Here, we aimed to generate adipocytes expressing a constitutively active CPT1A form (CPT1AM) that can improve the obese phenotype in mice after their implantation. AT-MSCs were differentiated into mature adipocytes, subjected to lentivirus-mediated expression of CPT1AM or the GFP control, and subcutaneously implanted into mice fed a high-fat diet (HFD). CPT1AM-implanted mice showed lower body weight, hepatic steatosis and serum insulin and cholesterol levels alongside improved glucose tolerance. HFD-induced increases in adipose tissue hypertrophy, fibrosis, inflammation, endoplasmic reticulum stress and apoptosis were reduced in CPT1AM-implanted mice. In addition, the expression of mitochondrial respiratory chain complexes was enhanced in the adipose tissue of CPT1AM-implanted mice. Our results demonstrate that implantation of CPT1AM-expressing AT-MSC-derived adipocytes into HFD-fed mice improves the obese metabolic phenotype, supporting the future clinical use of this ex vivo gene therapy approach.
Insights
Engineered adipocytes expressing active Carnitine palmitoyltransferase 1A (CPT1A) improved obesity and metabolic dysfunction in mice. This cell therapy approach offers a promising strategy for treating metabolic diseases.
Area of Science:
- Metabolic research
- Cell therapy
- Obesity research
Background:
- Obesity and metabolic comorbidities are a growing global concern, necessitating innovative therapeutic strategies.
- Adipose tissue and its derived mesenchymal stem cells (AT-MSCs) are crucial for energy balance and hold potential for cell-based therapies.
- Carnitine palmitoyltransferase 1A (CPT1A) regulates mitochondrial fatty acid oxidation, a key metabolic process.
Purpose of the Study:
- To develop and evaluate adipocytes engineered to express a constitutively active form of CPT1A (CPT1AM) for potential treatment of obesity.
- To assess the efficacy of implanting these CPT1AM-expressing adipocytes in a mouse model of diet-induced obesity.
Main Methods:
- Adipose tissue-derived mesenchymal stem cells (AT-MSCs) were differentiated into adipocytes.
- Lentivirus-mediated gene transfer was used to express CPT1AM or a GFP control in adipocytes.
- These engineered adipocytes were subcutaneously implanted into mice fed a high-fat diet (HFD).
Main Results:
- CPT1AM-implanted mice exhibited reduced body weight, hepatic steatosis, serum insulin, and cholesterol levels compared to controls.
- Improved glucose tolerance was observed in mice receiving CPT1AM-expressing adipocytes.
- HFD-induced adipose tissue abnormalities, including hypertrophy, fibrosis, inflammation, ER stress, and apoptosis, were ameliorated.
- Mitochondrial respiratory chain complex expression was upregulated in the adipose tissue of CPT1AM-treated mice.
Conclusions:
- Implantation of CPT1AM-expressing AT-MSC-derived adipocytes effectively improves the metabolic phenotype in diet-induced obese mice.
- This ex vivo gene therapy approach demonstrates therapeutic potential for obesity and related metabolic disorders.
- The findings support the future clinical translation of this strategy for metabolic disease treatment.
