RESUMEN

INTRODUCTION: Several studies demonstrated that deferoxamine, an iron chelator, can improve inflammatory alterations in adipose tissue induced by obesity. Obesity alterations in adipose tissue are also associated with tissue remodeling, and deferoxamine has anti-fibrosis action previously described in sites like the skin and liver. METHODS: In this work, we analyzed deferoxamine effects on adipose tissue fibro-inflammation during obesity induced by diet in mice. in vitro approaches with fibroblasts and macrophages were also carried out to elucidate deferoxamine activity. RESULTS: Our results demonstrated that in addition to exerting anti-inflammatory effects, reducing the cytokine production in adipose tissue of obese mice and by human monocyte differentiated in macrophage in vitro, deferoxamine can alter metalloproteinases expression and extracellular matrix production in vivo and in vitro. CONCLUSION: Deferoxamine could be an alternative to control fibro-inflammation in obese adipose tissue, contributing to the metabolic improvements previously described.

Asunto(s)

Deferoxamina , Resistencia a la Insulina , Humanos , Animales , Ratones , Deferoxamina/farmacología , Deferoxamina/uso terapéutico , Deferoxamina/metabolismo , Tejido Adiposo , Obesidad/metabolismo , Inflamación/metabolismo , Hígado/metabolismo , Ratones Endogámicos C57BL

RESUMEN

Extracellular matrix (ECM) remodeling is necessary for a health adipose tissue (AT) expansion and also has a role during weight loss. We investigate the ECM alteration during weight cycling (WC) in mice and the role of matrix metalloproteinases (MMPs) was assessed using GM6001, an MMP inhibitor, during weight loss (WL). Obesity was induced in mice by a high-fat diet. Obese mice were subject to caloric restriction for WL followed by reintroduction to high-fat diet for weight regain (WR), resulting in a WC protocol. In addition, mice were treated with GM6001 during WL period and the effects were observed after WR. Activity and expression of MMPs was intense during WL. MMP inhibition during WL results in inflammation and collagen content reduction. MMP inhibition during WL period interferes with the period of subsequent expansion of AT resulting in improvements in local inflammation and systemic metabolic alterations induced by obesity. Our results suggest that MMPs inhibition could be an interesting target to improve adipose tissue inflammation during WL and to support weight cyclers.

Asunto(s)

Dipéptidos/farmacología , Matriz Extracelular/metabolismo , Grasa Intraabdominal/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Obesidad/enzimología , Animales , Restricción Calórica , Colágeno/genética , Colágeno/metabolismo , Dieta Alta en Grasa/efectos adversos , Metabolismo Energético , Matriz Extracelular/efectos de los fármacos , Expresión Génica , Inflamación/prevención & control , Grasa Intraabdominal/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Metaloproteinasa 12 de la Matriz/genética , Metaloproteinasa 12 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/genética , Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Obesidad/etiología , Obesidad/genética , Obesidad/patología , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Aumento de Peso/efectos de los fármacos , Pérdida de Peso/efectos de los fármacos