The Mechanism Of White Fat Browning Promoting Wound Healing Through M2 Polarization Of Macrophages And Fibroblast Proliferation

BackgroundChronic wounds seriously affect the quality of life of patients,bring a heavy burden to individuals,society,and medical systems,and are medical problems that urgently need to be resolved.Tissue repair after trauma is a complex and delicate physiological process that requires the cooperation of a variety of cells and cytokines.Adipocytes are one of the most abundant cells under the skin.Adipocytes can participate in wound healing through lipolysis,transdifferentiation into fibroblasts,secretion of antimicrobial peptides,and promotion of wound hemostasis.Our previous studies have found that fat transplantation can inhibit inflammation and promote the healing of diabetic wounds,but the changes in fat cells and the mechanism of promoting wound healing are not yet clear.The browning of white fat is the adaptive change of fat cells in response to cold and other stimuli,and is an important target for promoting energy expenditure and treating metabolic-related diseases.However,the role of fat browning in the wound healing process is not yet clear.This study will use mouse normal and diabetic wound models to explore the role of fat browning in the wound healing process by adjusting the level of fat browning up and down,and to explore the mechanism of fat browning affecting wound healing through in vitro experiments.Methods1.Observe the changes of subcutaneous fat cells during wound healing.Make normal and diabetic wounds in mice,observe the post-traumatic subcutaneous fat morphology,gene transcription level,protein level and metabolic changes.2.Exploring the effect of up-down regulation of subcutaneous fat browning level on wound healing.CL316243 and rapamycin were used to adjust the level of fat browning respectively,and the changes in healing rate,collagen synthesis,macrophage infiltration,and wound inflammation levels were observed.3.Exploring the effects of white fat and beige fat on cells related to wound healing in vitro.White and beige adipocytes were co-cultured with fibroblasts and macrophages to detect the effect of fat browning on cells related to wound healing.Results1.After skin tissue trauma,the subcutaneous fat browned,and the level increased significantly during the wound healing period,and then decreased to normal after the wound was healed.The level of fat browning was impaired in the diabetic wound model.2.Increasing the level of fat browning will promote the synthesis of wound collagen,recruit M2 macrophages,inhibit wound inflammation,and promote wound healing;inhibiting the browning of fat under the wound will block collagen synthesis,increase subcutaneous fat necrosis,promote wound inflammation,and form chronic wounds.Hard to heal wounds.3.Beige adipocyte secretion factors can promote the proliferation and migration of fibroblasts,and recruit M2 type macrophages.ConclusionThe browning of white fat can promote the proliferation and migration of fibroblasts by secreting factors,and promote the infiltration of M2 macrophages.The browning of white fat can make fat cells resist the inflammatory and necrotic signals in the wound microenvironment.Damage to the browning of white fat will lead to increased fat necrosis after trauma,increase the level of inflammation in the wound microenvironment,and promote the apoptosis of fibroblasts and the infiltration of M1 macrophages.In the diabetic wound environment,the browning ability of white fat is impaired,and fat necrosis increases.The promotion of browning can promote the healing of diabetic wounds.