Transplantation of fat tissues and iPSC-derived energy expenditure adipocytes to counteract obesity-driven metabolic disorders: Current strategies and future perspectives

Abstract

Several therapeutic options have been developed to address the obesity epidemic and treat associated metabolic diseases. Despite the beneficial effects of surgery and drugs, effective therapeutic solutions have been held back by the poor long-term efficiency and detrimental side effects. The development of alternative approaches is thus urgently required. Fat transplantation is common practice in many surgical procedures, including aesthetic and reconstructive surgery, and is a budding future direction for treating obesity-related metabolic defects. This review focuses on adipose tissue transplantation and the recent development of cell-based therapies to boost the mass of energy-expenditure cells. Brown adipocyte transplantation is a promising novel therapy to manage obesity and associated metabolic disorders, but the need to have an abundant and relevant source of brown fat tissue or brown adipocytes for transplantation is a major hurdle to overcome. Current studies have focused on the rodent model to obtain a proof of concept of a tissue-transplantation strategy able to achieve effective long-term effects to reverse metabolic defects in obese patients. Future perspectives and opportunities to develop innovative human fat tissue models and 3D engineered hiPSC-adipocytes are discussed.

The Application and Efficacy Evaluation of Autologous Fat Transplantation in Antiaging of the Face: Systematic Review and Meta-Analysis

“…Increase the local solubility of adipose stem cells (ASC) to improve survival, as well as related cytokines, such as hypertrophic plasma (HP). It is used to improve vascular fat transplantation and reduce fibrosis and calcification [ 22 ].…”

Engineering Functional Vascularized Beige Adipose Tissue from Microvascular Fragments of Models of Healthy and Type II Diabetes Conditions

“…46,81,82 Lastly, the impact of transplanting these engineered beige adipose tissues subcutaneously has on whole-body metabolic hemostasis should be investigated. 27,83…”

Improved Vascularization and Survival of White Compared to Brown Adipose Tissue Grafts in the Dorsal Skinfold Chamber

“…However, the safety of this procedure is questionable, because WAT is a rich source of endothelial progenitor cells and, thus, may markedly contribute to the formation and vascularization of new breast cancer lesions [ 23 , 24 , 25 ]. Due to their positive impact on metabolism, fat grafts have additionally emerged over the last decades as an innovative treatment option for obesity-related metabolic pathologies [ 12 ]. Contrary to WAT grafts, which mainly improve glucose tolerance or insulin sensitivity, BAT grafts may also aid in decreasing excessive fat storage and targeting obesity directly by increasing the organism’s energy expenditure and heat production [ 15 , 16 , 26 ].…”

“…This may be achieved by inducing transient browning of adipocytes using phytochemicals [ 10 , 11 ]. Another highly promising approach is the transplantation of WAT or BAT [ 12 ]. The grafting of WAT is aimed at harnessing its beneficial effects regarding lipogenesis, fatty acid oxidation, or adipokine secretion as well as its high capacity to prevent detrimental ectopic lipid storage [ 13 ].…”