Metabolism, Morphology, and Effect of Fat Grafts - Studies on Fat Graft Browning and Therapeutic Use in the Prevention of Peritoneal Adhesions

Abstract

BACKGROUND: Fat transfer is a basic technique in the field of plastic surgery, but so far, there is very little information about what happens to fat grafts after transfer. The aim of this dissertation was to determine whether the metabolically inactive white adipose tissue (WAT) used in fat grafts is transformed in the recipient area in the direction of thermogenic brown adipose tissue (BAT), referred to as beige adipose tissue (Study I and III). Adipose tissue has anti-inflammatory and pro-healing properties, which we used to determine whether fat transfer can prevent peritoneal adhesions after open abdominal surgery.

METHODS: In Study I, we investigated changes in subcutaneous and intramuscular WAT grafts using PET/CT (18F-fluorodeoxyglucose(FDG) as a tracer), histology, and BAT-related Ucp1 gene expression in a mouse model. Using a mouse model, we also performed 18F-FDG-PET/CT imaging, clinical analysis, histology, and macrophage phenotyping to determine whether fat graft transfer to the injured area of the peritoneum can prevent the formation of adhesions (study II). In Study III, we used 18F-FDG-PET/MRI imaging (in cold and warm temperatures) to study the metabolic activity of the fat graft area and the histology of the tissue samples from patients who previously received fat grafts.

RESULTS: In study I, we found that some intramuscular fat grafts had transformed in terms of morphology and gene expression in the direction of BAT, as a sign of browning of WAT. In study II, we found that fewer adhesions were formed in the fat graft group, and that they were looser in structure compared to the adhesion group without fat. In addition, inflammatory activity was lower. In Study III, a cold-induced increase in glucose metabolism, typical of BAT, was found in the fat graft areas.

CONCLUSION: Fat grafts may transform into more metabolically active beige fat as a result of browning, which is indicated by both the tissue samples and the increase in Ucp1 gene expression (study I) and the metabolic changes after cold exposure detected by PET imaging (study III). Fat grafts can prevent the formation of peritoneal adhesions in a mouse model (Study II).