Illawarra Health and Medical Research Institute and School of Medicine, University of Wollongong, NSW2522, Australia.
Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, China.
Life Sci. 2020 Sep 15;257:118036. doi: 10.1016/j.lfs.2020.118036. Epub 2020 Jul 2.
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.
已报道 n-3 多不饱和脂肪酸（n-3PUFAs）具有抗肥胖作用，并能提高瘦素敏感性，在饮食诱导肥胖的动物中。本研究旨在确定二十二碳六烯酸（DHA，22:6n-3）在高脂肪（HF）饮食喂养的小鼠中的有益的中枢作用和机制。
雄性 C57BL/6J 小鼠给予 HF 饮食，或同时给予脑室内（icv）注射二十二碳六烯酸（DHA，22:6n-3）两天。通过中枢性瘦素敏感性试验和 Western blot 检测中枢性瘦素敏感性、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 检测肝脏参与脂质代谢的基因表达。
我们发现，脑室内给予 DHA 不仅减少了能量摄入和体重增加，而且纠正了 HF 饮食引起的下丘脑炎症。DHA 降低了瘦素信号抑制剂 SOCS3，并改善了下丘脑的瘦素 JAK2-Akt 信号通路。此外，脑室内给予 DHA 改善了瘦素对肝脏中与脂肪生成、脂肪酸β-氧化和胆固醇合成相关的酶的 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 浓度可能防止下丘脑调节缺陷，这与高脂肪饮食导致的肝脏能量平衡紊乱有关。
