Inhibition of Adipocyte-Derived FABP4 Reduces Adipocyte Inflammation, Improves Angiogenesis, and Facilitates Wound Healing in Metabolic Dysfunctions

Abstract

Dermal white adipose tissue may participate in the wound healing process. Obesity-mediated chronic low-grade inflammation impairs wound healing by suppressing vascularity. Given that fatty-acid-binding protein (FABP) 4 is upregulated in the skin tissue of obese animals, this study aimed to investigate the effects of FABP4 inhibition on wound healing in high-fat-diet (HFD)-induced metabolic dysfunction mice in vivo. The interaction between adipocyte-derived FABP4 and vascular endothelial cell function was also investigated. In HFD-induced metabolic dysfunction mice, FABP4 inhibition increased angiogenesis and facilitated wound healing with reduced wound inflammation. FABP4 inhibition not only attenuated systemic inflammation, decreased body weight, and reduced insulin resistance, but also improved the sizes of adipocytes and hypoxic conditions in dermal white adipose tissue. The in vitro hypoxia was used to induce adipocyte inflammation, and the supernatants from hypoxia-stimulated adipocytes impaired the function and angiogenetic capability of human dermal microvascular endothelial cells. Both of them were improved by FABP4 inhibition. Altogether, FABP4 inhibition reduced systemic and adipocyte inflammation, improved vascular endothelial cell function, and facilitated wound healing in metabolic dysfunctions. Given the complex involvement of wound healing, future studies may be required to validate FABP4 as a potential therapeutic target for wound repair in metabolic dysfunctions.