The skin serve as the first line of defense against physical or biological damage, with the ability to self-repair following injury [1]. Disruption of skin integrity activates a cascade of cellular and molecular events, initiating an inflammatory response, tissue hemostasis, and immune cell recruitment. This is followed by fibroblast proliferation, angiogenesis, and re-epithelialization, ultimately leading to tissue remodeling and maturation [2]. While this sequence of events occurs consistently in most skin wounds, failures in cellular and signaling cross-talk can arise at any stage of healing, particularly in the presence of systemic conditions [3]. Despite the extensive investigation into the skin repair process under both healthy and diseased conditions, some critical molecular aspects remain to be fully elucidated.

Addressing chronic wounds remains a significant clinical challenge due to the limited effectiveness and high costs associated with current therapeutic options [4,5]. Consequently, strategies to enhance wound repair are an emerging focus in biomedical science. Photobiomodulation therapy (PBMT) is increasingly applied to various medical conditions [6], recognized for its non-invasive, painless, and highly versatile nature. PBMT has demonstrated potential to modulate inflammatory responses, enhance cellular viability and proliferation, promote re-epithelialization, stimulate microcirculation, and exert antibacterial effects within wounds [7]. However, the precise mechanistic pathways through which PBMT facilitates wound healing are yet to be comprehensively understood.

Adipose tissue has emerged as a systemically significant player in physiopathology, particularly in its crucial role in wound regeneration [8,9]. Adipocytes acts as endocrine components, secreting cytokines and growth factors, while their precursor cells proliferate and mature into intradermal adipocytes that repopulate the skin after wounding [8,10]. A groundbreaking study revealed a mechanism whereby adipocyte lipolysis influences inflammation regulation and wound repair. Adipocytes near an injury release lipids essential for macrophage infiltration. Subsequently, dermal adipocytes alter their fate to become extracellular matrix-producing myofibroblasts within wounds [9]. Pharmacological and genetic inhibition of adipocytes disrupts fibroblast presence and extracellular matrix protein deposition in the regenerating dermis [8]. Consequently, adipocytes represent potential therapeutic targets for inflammatory diseases like diabetes, which are associated with defective wound healing [8].

A study recently demonstrated that PBMT effectively reduces excessive free fatty acid (FA) generation and release in models of Type 2 diabetes and obesity [11]. PBMT triggered reactive oxygen species (ROS) generation, which indirectly inhibited the transcriptional activity of Forkhead box transcription factor O1 (FoxO1), thereby reducing the expression of lipolytic enzymes and FA release [11]. However, to the best of our knowledge, no study has comprehensively examined the molecular effects of PBMT on dermal mature adipocytes following wounding in healthy individuals. Additionally, there is limited understanding of PBMT's implications for lipolysis and lipogenesis events in the dermis, particularly in the context of skin wounds. The aim of this study was to evaluate the outcomes of PBMT stimulation on adipocytes present in skin wounds produced in vitro, ex vivo and in vivo.