Instituto Tecnológico Superior de Tacámbaro, Michoacán, México.
Facultad de Químico-Farmacobiología, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, México.
Nutr Neurosci. 2023 Jan;26(1):25-39. doi: 10.1080/1028415X.2021.2012629. Epub 2021 Dec 14.
Obesity results from an unbalance in the ingested and burned calories. Energy balance (EB) is critically regulated by the hypothalamic arcuate nucleus (ARC) by promoting appetite or anorectic actions. Hypothalamic inflammation, driven by high activation of the microglia, has been reported as a key mechanism involved in the development of diet-induced obesity. Kaempferol (KF), a flavonoid-type polyphenol present in a large number of fruits and vegetables, was shown to regulate both energy metabolism and inflammation.
In this work, we studied the effects of both the central and peripheral treatment with KF on hypothalamic inflammation and EB regulation in mice with obesity.
Obese adult mice were chronically (40 days) treated with KF (0.5 mg/kg/day, intraperitoneally). During the treatment, body weight, food intake (FI), feed efficiency (FE), glucose tolerance, and insulin sensitivity were determined. Analysis of microglia activation in the ARC of the hypothalamus at the end of the treatment was also performed. Body weight, FI, and FE changes were also evaluated in response to 5µg KF, centrally administrated.
Chronic administration of KF decreased ∼43% of the density, and ∼30% of the ratio, of activated microglia in the arcuate nucleus. These changes were accompanied by body weight loss, decreased FE, reduced fasting blood glucose, and a tendency to improve insulin sensitivity. Finally, acute central administration of KF reproduced the effects on EB triggered by peripheral administration.
These findings suggest that KF might fight obesity by regulating central processes related to EB regulation and hypothalamic inflammation.
肥胖是由于摄入的卡路里和燃烧的卡路里之间失去平衡造成的。能量平衡（EB）由下丘脑弓状核（ARC）严格调节，通过促进食欲或厌食作用。已经报道，由小胶质细胞高度激活引起的下丘脑炎症是参与饮食诱导肥胖发展的关键机制之一。山奈酚（KF），一种存在于大量水果和蔬菜中的类黄酮型多酚，被证明可以调节能量代谢和炎症。
在这项工作中，我们研究了 KF 对肥胖小鼠下丘脑炎症和 EB 调节的中枢和外周治疗的影响。
肥胖成年小鼠接受 KF（0.5mg/kg/天，腹腔内）慢性（40 天）治疗。在治疗过程中，测定体重、食物摄入量（FI）、饲料效率（FE）、葡萄糖耐量和胰岛素敏感性。还分析了治疗结束时下丘脑 ARC 中小胶质细胞激活的情况。还评估了对中央给予的 5μg KF 时体重、FI 和 FE 变化的反应。
慢性 KF 给药可使弓状核中活化小胶质细胞的密度降低约 43%，比率降低约 30%。这些变化伴随着体重减轻、FE 降低、空腹血糖降低以及改善胰岛素敏感性的趋势。最后，急性中央给予 KF 再现了外周给予 KF 对 EB 产生的影响。
这些发现表明，KF 可能通过调节与 EB 调节和下丘脑炎症相关的中枢过程来对抗肥胖。
