Fructose 1,6-Bisphosphate as a Protective Agent for Experimental Fat Grafting

Abstract

Fat grafting procedures are considered to be a promising regenerative, cell‐directed therapy; however, their survival is mainly influenced by ischemia condition. Fructose 1,6‐bisphosphate (FBP), as an intermediate in energy metabolism, has the potential to rescue cells and tissues from hypoxic‐ischemic circumstances. In the present study, human lipoaspirates were grafted subcutaneously into nude mice followed by a daily intraperitoneal injection of FBP at different doses for 7 days. Next, the grafts were harvested at different time points till 12 weeks postimplantation and were evaluated for cell viability and function, tissue revascularization and inflammatory cell infiltration using histological analysis, whole‐mount living tissue imaging, glycerol 3‐phosphate dehydrogenase activity assays, and quantitative analysis of gene expression. The results demonstrated that exogenous FBP administration could attenuate the volume and weight reduction of fat graft; meanwhile, FBP enhanced adipocyte viability and function, increased blood vessel formation, and decreased inflammation. Moreover, in vitro cell experiments showed that FBP could promote adipose‐derived stem cell viability and vascular endothelial growth factor (VEGF) mRNA expression in ischemia conditions. Our study indicates that FBP can be used as a protective agent for fat grafting and may be applied in stem cell‐based regenerative medicine. stem cells translational medicine 2019;8:606–616

The metabolic characteristic of decidual immune cells and their unique properties in pregnancy loss*

“…shown multiple protective properties including anti-fibrotic, antiinflammatory, anti-convulsant, and immunomodulatory effects. 114 Being the first rate-limiting enzymes in the glycolytic pathway, PFK1…”

“…This specific metabolic milieu may influence macrophage function indirectly. Fructose‐1,6‐bisphosphate (FBP), an endogenous intracellular metabolite in the glycolytic pathway produced by phosphofructokinase‐1 (PFK1), has shown multiple protective properties including anti‐fibrotic, anti‐inflammatory, anti‐convulsant, and immunomodulatory effects 114 . Being the first rate‐limiting enzymes in the glycolytic pathway, PFK1 would catalyze the phosphorylation of fructose‐6‐phosphate (F‐6‐P) to fructose 1,6‐bisphosphate (F‐1,6‐2P) using adenosine triphosphate (ATP), whereas fructose bisphosphatase‐1 (FBP1) would mediate the conversion of F‐1,6‐2P into F‐6‐P in the gluconeogenic pathway.…”

Regulation of Glucose Metabolism for Cell Energy Supply In Situ via High‐Energy Intermediate Fructose Hydrogels

“…[27][28][29][30] Previous research has demonstrated the benefits of FBP for treating ischemia myocardia, promoting the survival of transplanted adipose tissue, maintaining bone homeostasis, and safeguarding hypoxia reperfusion ECs. [31][32][33][34][35][36] Therefore, it is a more efficient option to use high-energy intermediate FBP to directly supply energy to damaged tissue cells. However, FBP was originally administered intravenously in huge dosages without any targeting, which may lead to lactic acid poisoning, increased uric acid and other risks, and even life-threatening, and it is also challenging to maintain effective concentration when used locally.…”

LRG‐1 promotes fat graft survival through the RAB31‐mediated inhibition of hypoxia‐induced apoptosis

“…Before neovascularization develops, the graft must face a period of hypoxia, so other researchers thought that the resilience of adipocytes to hypoxia and relative macrophage activation play crucial roles in fat graft retention. 11 , 12 , 13 Adipocytes are sensitive to stress and hypoxia, which are the two major obstacles in large‐volume fat grafting. 14 Researchers found that apoptosis induced by many factors in the graft environment such as hypoxia and inflammation is a cause of long‐term volume reduction of the fat graft.…”

“…Therefore, these methods have limited effects in improving the survival of transplanted fat and cannot be used in clinical applications. Before neovascularization develops, the graft must face a period of hypoxia, so other researchers thought that the resilience of adipocytes to hypoxia and relative macrophage activation play crucial roles in fat graft retention 11–13 . Adipocytes are sensitive to stress and hypoxia, which are the two major obstacles in large‐volume fat grafting 14 .…”