Obesity is a major health problem worldwide. Overweight and obesity directly affect health-related quality of life and also have an important economic impact on healthcare systems. In experimental models, obesity leads to hypothalamic inflammation and loss of metabolic homeostasis. It is known that macroautophagy is decreased in the hypothalamus of obese mice but the role of chaperone-mediated autophagy is still unknown. In this study, we aimed to investigate the role of hypothalamic chaperone-mediated autophagy in response to high-fat diet and also the direct effect of palmitate on hypothalamic neurons. Mice received chow or high-fat diet for 3 days or 1 week. At the end of the experimental protocol, chaperone-mediated autophagy in hypothalamus was investigated, as well as cytokines expression. In other set of experiments, neuronal cell lines were treated with palmitic acid, a saturated fatty acid. We show that chaperone-mediated autophagy is differently regulated in response to high-fat diet intake for 3 days or 1 week. Also, when hypothalamic neurons are directly exposed to palmitate there is activation of chaperone-mediated autophagy. High-fat diet causes hypothalamic inflammation concomitantly to changes in the content of chaperone-mediated autophagy machinery. It remains to be studied the direct role of inflammation and lipids itself on the activation of chaperone-mediated autophagy in the hypothalamus in vivo and also the neuronal implications of chaperone-mediated autophagy inhibition in response to obesity.

肥胖是世界范围内的主要健康问题。超重和肥胖直接影响与健康相关的生活质量，并对医疗保健系统产生重要的经济影响。在实验模型中，肥胖会导致下丘脑发炎并失去代谢稳态。众所周知，肥胖小鼠下丘脑中的巨噬自噬减少，但伴侣蛋白介导的自噬的作用仍是未知的。在这项研究中，我们旨在调查下丘脑伴侣介导的自噬对高脂饮食的作用，以及棕榈酸酯对下丘脑神经元的直接作用。小鼠接受食物或高脂饮食持续3天或1周。在实验方案的最后，研究了下丘脑中伴侣介导的自噬以及细胞因子的表达。在另一组实验中 用棕榈酸，一种饱和脂肪酸处理神经元细胞系。我们显示，伴侣脂肪介导的自噬在3天或1周内对高脂饮食摄入的反应不同。同样，当下丘脑神经元直接暴露于棕榈酸酯时，会激活伴侣介导的自噬。高脂饮食会导致下丘脑炎症，并伴随伴侣蛋白介导的自噬机制含量的变化。炎症和脂质本身对下丘脑中伴侣介导的自噬激活的直接作用仍有待研究 当下丘脑神经元直接暴露于棕榈酸酯时，会激活伴侣介导的自噬。高脂饮食会导致下丘脑炎症，并伴随伴侣蛋白介导的自噬机制含量的变化。炎症和脂质本身在下丘脑中伴侣介导的自噬激活中的直接作用仍有待研究 当下丘脑神经元直接暴露于棕榈酸酯时，会激活伴侣介导的自噬。高脂饮食会导致下丘脑炎症，并伴随伴侣蛋白介导的自噬机制含量的变化。炎症和脂质本身在下丘脑中伴侣介导的自噬激活中的直接作用仍有待研究在体内以及伴侣对肥胖的响应中伴侣蛋白介导的自噬抑制的神经元影响。