Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.
Neurometabolomics Research Center, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.
Mol Brain. 2021 Apr 6;14(1):65. doi: 10.1186/s13041-021-00777-8.
Palmitate is a saturated fatty acid that is well known to induce endoplasmic reticulum (ER) stress and autophagy. A high-fat diet increases the palmitate level in the hypothalamus, the main region of the brain regulating energy metabolism. Interestingly, hypothalamic palmitate level is also increased under starvation, urging the study to distinguish the effects of elevated hypothalamic palmitate level under different nutrient conditions. Herein, we show that ER-phagy (ER-targeted selective autophagy) is required for progress of ER stress and that palmitate decreases ER stress by inhibiting ER-phagy in hypothalamic cells under starvation. Palmitate inhibited starvation-induced ER-phagy by increasing the level of B-cell lymphoma 2 (Bcl-2) protein, which inhibits autophagy initiation. These findings suggest that, unlike the induction of ER stress under nutrient-rich conditions, palmitate protects hypothalamic cells from starvation-induced stress by inhibiting ER-phagy.
棕榈酸是一种饱和脂肪酸，已知其可诱导内质网（ER）应激和自噬。高脂肪饮食会增加下丘脑中的棕榈酸水平，而下丘脑是调节能量代谢的大脑主要区域。有趣的是，饥饿也会增加下丘脑中的棕榈酸水平，这促使人们研究在不同营养条件下升高的下丘脑中棕榈酸水平的影响。本文中，我们发现内质网自噬（内质网靶向选择性自噬）对于 ER 应激的进展是必需的，并且在饥饿条件下，棕榈酸通过增加 B 细胞淋巴瘤 2（Bcl-2）蛋白的水平抑制内质网自噬，从而降低 ER 应激。棕榈酸通过增加抑制自噬起始的 Bcl-2 蛋白的水平，抑制饥饿诱导的内质网自噬。这些发现表明，与营养丰富条件下诱导 ER 应激不同，棕榈酸通过抑制内质网自噬来保护下丘脑细胞免受饥饿诱导的应激。
