Anti-obesity effects and improved leptin sensitivity from n-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported in diet-induced obese animals. This study sought to determine the beneficial central effects and mechanism of docosahexaenoic acid (DHA, 22:6 n-3) in high-fat (HF) diet fed mice. Male C57BL/6J mice were given HF diet with or without intracerebroventricular (icv) injection of docosahexaenoic acid (DHA, 22:6 n-3) for two days. Central leptin sensitivity, hypothalamic inflammation, leptin signaling molecules and tyrosine hydroxylase (TH) were examined by central leptin sensitivity test and Western blot. Furthermore, the expression of hepatic genes involved in lipid metabolism was examined by RT-PCR. We found that icv administration of DHA not only reduced energy intake and body weight gain but also corrected the HF diet-induced hypothalamic inflammation. DHA decreased leptin signaling inhibitor SOCS3 and improved the leptin JAK2-Akt signaling pathways in the hypothalamus. Furthermore, icv administration of DHA improved the effects of leptin in the regulation of mRNA expression of enzymes related to lipogenesis, fatty acid β-oxidation, and cholesterol synthesis in the liver. DHA increased leptin-induced activation of TH in the hypothalamus. Therefore, increasing central DHA concentration may prevent the deficit of hypothalamic regulation, which is associated with disorders of energy homeostasis in the liver as a result of a high-fat diet.

中文翻译：

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DHA 可减轻小鼠下丘脑炎症并改善中枢瘦素信号传导

据报道，n-3 多不饱和脂肪酸 (n-3 PUFA) 在饮食诱导的肥胖动物中具有抗肥胖作用并改善瘦素敏感性。本研究旨在确定二十二碳六烯酸 (DHA, 22:6 n-3) 对高脂肪 (HF) 饮食喂养的小鼠的有益中枢作用和机制。雄性 C57BL/6J 小鼠接受 HF 饮食，伴或不伴脑室内 (icv) 注射二十二碳六烯酸 (DHA，22:6 n-3)，为期两天。通过中枢瘦素敏感性试验和Western blot检测中枢瘦素敏感性、下丘脑炎症、瘦素信号分子和酪氨酸羟化酶（TH）。此外，通过RT-PCR检查了参与脂质代谢的肝脏基因的表达。我们发现，静脉注射 DHA 不仅可以减少能量摄入和体重增加，还可以纠正 HF 饮食引起的下丘脑炎症。 DHA 减少瘦素信号抑制剂 SOCS3 并改善下丘脑的瘦素 JAK2-Akt 信号通路。此外，静脉注射DHA可改善瘦素对肝脏中脂肪生成、脂肪酸β-氧化和胆固醇合成相关酶mRNA表达的调节作用。 DHA 增加了瘦素诱导的下丘脑 TH 的激活。因此，增加中枢 DHA 浓度可以防止下丘脑调节缺陷，下丘脑调节缺陷与高脂肪饮食导致的肝脏能量稳态紊乱有关。