Low-dose diet supplement of a natural flavonoid, luteolin, ameliorates diet-induced obesity and insulin resistance in mice
Low-dose diet supplement of a natural flavonoid, luteolin, ameliorates diet-induced obesity and insulin resistance in mice
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天然类黄酮木犀草素的低剂量饮食补充剂可改善饮食引起的肥胖和小鼠胰岛素抵抗
DOI：
10.1002/mnfr.201300830
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发表时间：
2014-06-01
影响因子：
5.2
通讯作者：
Liu, Jian
中科院分区：
文献类型：
--
作者：
Xu, Na;Zhang, Lei;Liu, Jian
范围：肥大细胞在饮食诱导的肥胖和糖尿病中发挥重要作用，一些合成的肥大细胞稳定剂可以改善小鼠的相关代谢障碍。木犀草素(LU)是一种有效的天然肥大细胞稳定剂。然而，LU与这些常见代谢性疾病之间没有直接的相关性。方法和结果：雄性C57BL/6小鼠分别饲喂低脂饲料、高脂饲料、高脂饲料中添加0.002%和0.01%LU 12wk。饮食LU抑制高脂饮食诱导的体重增加、脂肪沉积和脂肪细胞肥大。同时，糖耐量和胰岛素敏感性也得到改善。有趣的是，饮食LU改善了附精脂肪组织中血管生成和相关细胞的凋亡和组织蛋白酶活性，这是肥大细胞参与饮食诱导的肥胖和糖尿病的一个关键机制。此外，我们还发现，饮食LU减少了附睾脂肪组织中肥大细胞和巨噬细胞的浸润以及炎症细胞因子的水平。最后，LU抑制肥大细胞来源的IL-6的表达，这是导致肥大细胞相关代谢紊乱的关键细胞因子，而蛋白激酶C激活剂佛波酯逆转了这种抑制作用。结论：作为一种天然黄酮类化合物，低剂量饮食补充LU改善了饮食诱导的肥胖和胰岛素抵抗，为这些疾病的治疗和干预提供了新的途径。
Scope: Mast cells play important roles in diet-induced obesity and diabetes, and some synthetic mast cell stabilizers can improve related metabolic disturbances in mice. Luteolin (LU) is a potent natural mast cell stabilizer. However, a direct correlation between LU and these common metabolic diseases is not established.Methods and results: Male C57BL/6 mice were fed low-fat diet, high-fat diet (HFD), HFD with 0.002 and 0.01% LU for 12 wk, respectively. Dietary LU suppressed HFD-induced body weight gain, fat deposition, and adipocyte hypertrophy. Meanwhile, glucose intolerance and insulin sensitivity was also improved. Interestingly, dietary LU ameliorated angiogenesis and associated cell apoptosis and cathepsin activity in epididymis adipose tissues, which is a critical mechanism that mast cells are involved in diet-induced obesity and diabetes. Further, we showed dietary LU reduced mast cell and macrophage infiltrations and inflammatory cytokine levels in epididymis adipose tissues. Finally, LU inhibited mast cell-derived IL-6 expression, which is a key cytokine that contributes to mast cell-associated metabolic derangements, and protein kinase C activator phorbol myristoyl acetate reversed the inhibitory effects.Conclusions: As a natural flavonoid, low-dose diet supplement of LU ameliorates diet-induced obesity and insulin resistance in mice, suggesting a new therapeutic and interventional approach for these diseases.