Effects of an High-Fat Diet Enriched in Lard or in Fish Oil on the Hypothalamic Amp-Activated Protein Kinase and Inflammatory Mediators.
Effects of an High-Fat Diet Enriched in Lard or in Fish Oil on the Hypothalamic Amp-Activated Protein Kinase and Inflammatory Mediators.
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DOI：
10.3389/fncel.2016.00150
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发表时间：
2016
影响因子：
5.3
通讯作者：
Monda M
中科院分区：
文献类型：
--
作者：
Viggiano E;Mollica MP;Lionetti L;Cavaliere G;Trinchese G;De Filippo C;Chieffi S;Gaita M;Barletta A;De Luca B;Crispino M;Monda M
富含猪油的高脂饮食（HFD）会诱发肥胖、炎症和氧化应激，而下丘脑核团的失调在这一机制中发挥着重要作用。参与食物摄入和炎症的一个重要因素是腺苷单磷酸依赖性激酶（AMPK），一种通过磷酸化激活的丝氨酸/苏氨酸激酶。欧米伽 (ω)3-多不饱和脂肪酸 (PUFA) 是已知可减轻肥胖相关疾病的膳食化合物，尽管其在下丘脑中作用的分子机制尚不完全清楚。我们假设 PUFA 的有益作用可能是由下丘脑中的 AMPK 介导的。为此，给大鼠喂食对照饮食 (CD) 或含有鱼油 (FD；富含 ω3-PUFA) 或猪油的等热量 HFD 6 周，并分析下丘脑中 AMPK 的激活、炎症状态（IKKβ、TNF-α）和氧化应激。此外，我们还研究了血清脂质谱、稳态模型评估（HOMA）指数和促炎参数。我们的结果显示，与 CD 喂养的大鼠相比，在 LD 喂养的大鼠的下丘脑水平，AMPK 激活、炎症和氧化应激增加，而在 FD 喂养的大鼠中未检测到任何变化。此外，与 LD 动物相比，FD 动物的体重增加、血脂谱、促炎参数和胰岛素抵抗均降低。总之，我们的数据表明，饮食中用不饱和脂肪酸替代饱和脂肪酸对调节肥胖下丘脑炎症和功能具有有益作用，在下丘脑水平上，胰岛素和/或瘦素抵抗、AMPK 激活和食欲亢进之间的相互作用是潜在的。
The high fat diet (HFD) rich in lard induces obesity, inflammation and oxidative stress, and the deregulation of hypothalamic nuclei plays an important role in this mechanism. One important factor involved in the food intake and inflammation is adenosine monophosphate-dependent kinase (AMPK), a serine/threonine kinase activated by phosphorylation. Omega (ω)3-polyunsaturated fatty acids (PUFA) are dietary compounds known to attenuate the obesity-related diseases, although the molecular mechanisms underlying their actions in the hypothalamus are not completely understood. We hypothesized that the beneficial effects of PUFA may be mediated by AMPK in the hypothalamus. To this aim, rats were fed a control diet (CD), or isocaloric HFD containing either fish oil (FD; rich in ω3-PUFA) or lard for 6 weeks, and the activation of AMPK, inflammatory state (IKKβ, TNF-α) and oxidative stress were analyzed in the hypothalamus. In addition, we also studied serum lipid profile, homeostatic model assessment (HOMA) index, and pro-inflammatory parameters. Our results showed, at the hypothalamic level of LD-fed rats, an increase of AMPK activation, inflammation and oxidative stress, while no modifications were detected in FD-fed animals compared to CD. In addition body weight gain, serum lipid profile, pro-inflammatory parameters and insulin resistance were reduced in FD animals compared to LD. In conclusion, our data indicate that the substitution of saturated by unsaturated fatty acids in the diet has beneficial effects on modulation of hypothalamic inflammation and function in obesity, underlying, at hypothalamic level, the interaction among insulin and/or leptin resistance, AMPK activation and hyperphagia.