The Browning and Mobilization of Subcutaneous White Adipose Tissue Supports Efficient Skin Repair

Biochemistry Life Sciences Immunology Medicine Cell Biology
White Adipose Tissue Browning Wound Healing NRG4 Macrophage Polarization Myofibroblast Function

Browning of Subcutaneous White Adipose Tissue and Skin Repair Efficiency

Current scientific research reveals that the participation of various cells is essential in the process of skin repair and regeneration. Among these, adipocytes (fat cells) have attracted attention due to their primary role in energy storage and critical endocrine functions in the body. However, there are only a few studies on the role of subcutaneous white adipose tissue (SWAT) in skin repair, and its mechanism remains unclear. Recently, Junrong Cai and his team conducted an in-depth study on the dynamic changes of SWAT during the wound healing process, revealing the important role of this adipose tissue in trauma repair.

Source of the Paper

This paper was completed by Junrong Cai, Yuping Quan, Shaowei Zhu, and others, primarily from the Department of Plastic and Cosmetic Surgery at Nanfang Hospital, Southern Medical University. The paper was published in the June 2024 issue of the journal Cell Metabolism.

Research Background and Issues

Adipocytes are important for energy storage and are considered to play a key role in tissue repair. Although previous studies have focused on dermal white adipose tissue (DWAT), the role of SWAT in skin repair remains unknown. Particularly, under conditions such as cold exposure or illness, SWAT undergoes “browning,” similar to the characteristics of brown adipose tissue (BAT). However, it is still unclear whether the browning of SWAT after injury can promote skin repair. Researchers hope that this study can reveal whether SWAT undergoes browning after trauma and its specific role in skin repair.

Overview of the Research Process

The research team conducted experiments primarily using mouse models, with the process including the following steps:

  1. Wound Model Design and Dynamic Observation of Adipose Tissue: Researchers created full-thickness skin wounds of 2mm, 4mm, and 6mm in the groin area of mice to observe the impact of different wound sizes on SWAT’s involvement in skin repair. They monitored the migration and performance of adipocytes at the wound site using staining techniques such as Dii staining and GFP labeling.

  2. Gene Tracking and Transgenic Models: Using gene tracking technology and the AdipoqCreER; mt/mG mouse model, the behavior of SWAT during the wound healing process was studied, with a focus on its potential transdifferentiation into fibroblasts.

  3. SWAT Browning Analysis: Human and mouse wound tissue samples were collected and analyzed using various methods (such as transmission electron microscopy, RT-qPCR, and Western Blot) to study changes in SWAT after injury, particularly the browning process of adipocytes and their role in wound repair.

  4. Gene Interference and Drug Experiments: The study used gene strategies to selectively reduce the expression of specific browning genes (such as Prdm16) in SWAT and observed the effects on the wound healing process. Additionally, drugs were used to activate or inhibit browning to observe their effects on wound healing.

Main Research Results

  1. SWAT Significantly Participates in the Repair of Large Wounds After Skin Injury: In the full-thickness wound model, SWAT significantly migrated to the wound bed of 6mm diameter wounds and participated in the formation of granulation tissue before wound closure. However, no significant SWAT migration was observed in smaller wounds (2mm and 4mm). This suggests that SWAT is primarily involved in the repair of large wounds.

  2. SWAT Undergoes Browning After Injury, and Inhibiting Browning Delays Wound Healing: A series of staining and gene analyses revealed that in healthy mice, SWAT exhibited multiple lipid droplets and high expression of uncoupling protein 1 (UCP-1) after injury, indicating browning. Inhibiting SWAT browning through gene interference significantly delayed the wound healing process.

  3. NRG4 Secreted by Browning SWAT Regulates Macrophage Polarization and Fibroblast Function: Gene expression analysis showed that NRG4, which is abundant in browning SWAT, promotes wound healing by affecting macrophage polarization and fibroblast function. The application of NRG4 significantly accelerated wound healing and enhanced re-epithelialization and granulation tissue thickness.

  4. SWAT Browning is Inhibited in Diabetic Mice, Leading to Significantly Delayed Wound Healing: The study showed that in diabetic mice, SWAT browning was significantly inhibited, resulting in reduced granulation tissue formation and delayed re-epithelialization in wounds. Although drug-induced browning of SWAT did not significantly improve wound healing, the application of NRG4 accelerated wound healing in diabetic mice.

Research Significance and Value

This study systematically reveals for the first time the important role of SWAT in skin repair, especially its involvement in the repair of large wounds and its mechanism of regulating macrophage and fibroblast functions through browning. This discovery not only provides a new perspective on the role of adipose tissue in wound healing but also offers a potential new therapeutic target for populations with difficulty in wound healing, such as those with diabetes, with significant scientific and practical value.

Research Highlights

  1. Revealing the Key Role of SWAT in Skin Healing: Using a mouse model, this study demonstrates for the first time that SWAT significantly participates in the repair of large wounds.

  2. Importance of SWAT Browning: The study proves that SWAT browning after injury is crucial for rapid wound healing, providing a new mechanism for adipose tissue in wound healing.

  3. Role of NRG4 in Wound Repair: The research found that NRG4 plays an important role in regulating wound healing, particularly in promoting macrophage polarization and fibroblast function. This provides strong scientific evidence for the future clinical application of NRG4.

Other Important Information

The study used various genetic and pharmacological methods, as well as a comparison of the different roles of SWAT and DWAT in wound healing, to provide rich data for further understanding the multiple functions of adipose tissue in trauma repair. Future research may focus on exploring other molecular mechanisms involved in SWAT browning and investigating its potential applications in other trauma and disease conditions.