Caria Cíntia Rabelo E Paiva, Gotardo Érica Martins Ferreira, Santos Paola Souza, Acedo Simone Coghetto, de Morais Thainá Rodrigues, Ribeiro Marcelo Lima, Gambero Alessandra
Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista, SP 12916-900, Brazil.
Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista, SP 12916-900, Brazil.
Exp Cell Res. 2017 Oct 15;359(2):431-440. doi: 10.1016/j.yexcr.2017.08.026. Epub 2017 Aug 19.
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.
细胞外基质（ECM）重塑对于健康的脂肪组织（AT）扩张是必要的，并且在体重减轻过程中也起作用。我们研究了小鼠体重循环（WC）期间的ECM变化，并在体重减轻（WL）期间使用MMP抑制剂GM6001评估了基质金属蛋白酶（MMPs）的作用。通过高脂饮食诱导小鼠肥胖。肥胖小鼠在WL期间接受热量限制，随后重新引入高脂饮食以恢复体重（WR），从而形成WC方案。此外，在WL期间用GM6001治疗小鼠，并在WR后观察效果。WL期间MMPs的活性和表达强烈。WL期间抑制MMP会导致炎症和胶原蛋白含量降低。WL期间抑制MMP会干扰随后AT扩张的时期，从而改善肥胖引起的局部炎症和全身代谢改变。我们的结果表明，抑制MMPs可能是改善WL期间脂肪组织炎症和支持体重循环者的一个有趣靶点。
