Alterações no reparo tecidual cutâneo em um modelo de resistência à insulina

Abstract

Obesity associated with with metabolic alterations such as insulin resistance causes significant modifications during the healing process. Our aim was initially to analyse the effects of insulin resistance induced by a high- significant changes in skin combined fat diet during cutaneous wound healing. And then investigate the role of macrophages in this process. We observed that animals subjected to a high-fat diet (HFC) became glucose intolerant and insulin resistant and increased plasma cholesterol and triglycerides levels when compared to animals fed with a standard chow (SC). The HFC group had a lower rate of wound contraction and re-epithelialization than the SC group. Besides, HFC group presented a greater number of inflammatory cells (NOS 2- and F4/80-positive cells, and neutrophils), lower density of collagen fibers and higher density of myofibroblasts and blood vessels. Oxidative damage was greater in the HFC group as well as the protein expression of TGF-β1 and α-smooth muscle actin (α- SMA). The HFC group presented higher levels of plasma TNF-α when compared to RP group. Furthermore, the proportion of M1 cells (classically activated macrophages) and M2 (alternatively activated macrophages) was the same in both groups. Regarding to the synthesis and release of cytokines and growth factors evaluated by in vitro assays, we also observed that the levels of TNF-α and IL-1β were higher in conditioned medium of macrophages isolated from animals of HFC (MCHFC) group when compared to the conditioned medium of macrophages isolated from animals in of RP (MCSC) group. Furthermore, our results clearly demonstrate that soluble factors produced by macrophages isolated from insulin resistant animals inhibit the proliferation and migration of fibroblasts. Thus, we can show that insulin resistance delays wound healing process and suggest that the macrophages are involved in this delay.