Valsartan restores inflammatory response by macrophages in adipose and hepatic tissues of LPS-infused mice.

Inflammation involving adipose tissue is regarded as one of the major molecular mechanisms underlying obesity-related insulin resistance. Recent studies have suggested a series of angiotensin II receptor blockers (ARBs) to improve insulin resistance or protect against the development of diabetes mellitus. We previously demonstrated that valsartan suppresses the inflammatory response of macrophages. Interestingly, however, this effect did not occur via peroxisome proliferator-activated receptor (PPAR) γ or the AT1a receptor. This suppression appears to secondarily lead to amelioration of insulin resistance and reductions in abnormal gene expressions in adipocytes. In addition to these in vitro findings, we herein demonstrate the in vivo effects of valsartan, using mice constitutively infused with lipopolysaccharide (LPS) for 4 weeks. Oral administration of valsartan to LPS-infused mice normalized the increased expressions of inflammatory cytokines in adipose and liver tissues. These results raise the possibility that valsartan not only contributes to normalization of obesity-related insulin resistance, but is also beneficial for the treatment of other diseases with inflammation related to the metabolic syndrome such as atherosclerosis and non-alcoholic steatohepatitis. Further study is necessary to clarify these issues.

脂肪组织炎症被视为肥胖相关胰岛素抵抗的主要分子机制之一。近期研究表明，一系列血管紧张素II受体阻滞剂（ARBs）可改善胰岛素抵抗或预防糖尿病的发生。我们先前已证实缬沙坦可抑制巨噬细胞的炎症反应。然而，有趣的是，这种作用并非通过过氧化物酶体增殖物激活受体（PPAR）γ或AT1a受体产生。这种抑制作用似乎进而导致胰岛素抵抗的改善以及脂肪细胞中异常基因表达的减少。除了这些体外研究结果外，我们在此利用连续4周注射脂多糖（LPS）的小鼠展示了缬沙坦的体内效应。给注射LPS的小鼠口服缬沙坦可使脂肪和肝脏组织中炎症细胞因子的升高表达恢复正常。这些结果增加了一种可能性，即缬沙坦不仅有助于肥胖相关胰岛素抵抗恢复正常，而且对治疗与代谢综合征相关的炎症性其他疾病，如动脉粥样硬化和非酒精性脂肪性肝炎也有益处。有必要进一步研究以阐明这些问题。