非诺贝特是一种降血脂过氧化物酶体增殖物激活受体 α (PPARα) 激动剂，临床上用于降低高胆固醇血症和高甘油三酯血症。我们研究了非诺贝特对高脂饮食 (HFD) 喂养的卵巢切除 (OVX) C57BL 中胰岛素抵抗和组织炎症的影响/6J小鼠，肥胖绝经后妇女的小鼠模型。雌性OVX小鼠被随机分为3组，接受低脂饮食、HFD或HFD补充0.05%（w/w）非诺贝特9周。使用血液分析、组织学分析、免疫组织化学和定量实时聚合酶链反应来测量胰岛素抵抗和组织炎症的参数。当给 HFD 喂养的 OVX 小鼠服用非诺贝特 9 周时，我们观察到体重增加、脂肪减少组织质量和内脏脂肪细胞的大小在食物摄入量没有变化的情况下。非诺贝特改善了这些小鼠的轻度高血糖、严重高胰岛素血症和葡萄糖耐量。它还将胰岛大小和胰岛素阳性 β 细胞面积减少到与低脂饮食喂养的 OVX 小鼠相似的水平。与此同时，非诺贝特的给药不仅抑制了胰腺脂质积累，而且还减少了胰腺和内脏脂肪组织中的 CD68 阳性巨噬细胞。非诺贝特治疗可降低脂肪组织中的肿瘤坏死因子 α (TNFα) mRNA 水平，并降低血清 TNFα 水平。这些结果表明，非诺贝特治疗可部分通过减少 HFD 喂养的 OVX 小鼠的组织炎症和 TNFα 表达来减轻胰岛素抵抗。© 2023。作者。

Fenofibrate is a hypolipidemic peroxisome proliferator-activated receptor α (PPARα) agonist used clinically to reduce hypercholesterolemia and hypertriglyceridemia.We investigated the effects of fenofibrate on insulin resistance and tissue inflammation in a high-fat diet (HFD)-fed ovariectomized (OVX) C57BL/6J mice, a mouse model of obese postmenopausal women.Female OVX mice were randomly divided into 3 groups and received a low-fat diet, an HFD, or an HFD supplemented with 0.05% (w/w) fenofibrate for 9 weeks. Parameters of insulin resistance and tissue inflammation were measured using blood analysis, histological analysis, immunohistochemistry, and quantitative real-time polymerase chain reaction.When fenofibrate was administered to HFD-fed OVX mice for 9 weeks, we observed reductions in body weight gain, adipose tissue mass, and the size of visceral adipocytes without the change of food intake. Fenofibrate improved mild hyperglycemia, severe hyperinsulinemia, and glucose tolerance in these mice. It also reduced pancreatic islet size and insulin-positive β-cell area to levels similar to those in OVX mice fed a low-fat diet. Concomitantly, administration of fenofibrate not only suppressed pancreatic lipid accumulation but also decreased CD68-positive macrophages in both the pancreas and visceral adipose tissue. Treatment with fenofibrate reduced tumor necrosis factor α (TNFα) mRNA levels in adipose tissue and lowered serum TNFα levels.These results suggest that fenofibrate treatment attenuates insulin resistance in part by reducing tissue inflammation and TNFα expression in HFD-fed OVX mice.© 2023. The Author(s).