Exposure to lipid mixture induces intracellular lipid droplet formation and impairs mitochondrial functions in astrocytes

IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemistry international Pub Date : 2024-06-14 DOI:10.1016/j.neuint.2024.105792
Yi-Chen Li, Jing-Ting Fu, Shun-Fen Tzeng
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Abstract

Astrocytes, the predominant glial cells in the central nervous system (CNS), play diverse roles including metabolic support for neurons, provision of neurotrophic factors, facilitation of synaptic neurotransmitter uptake, regulation of ion balance, and involvement in synaptic formation. The accumulation of lipids has been noted in various neurological conditions, yet the response of astrocytes to lipid-rich environments remains unclear. In this study, primary astrocytes isolated from the neonatal rat cortex were exposed to a lipid mixture (LM) comprising cholesterol and various fatty acids to explore their reaction. Our results showed that astrocyte viability remained unchanged following 24 h of 5% or 10% LM treatment. However, exposure to LM for 96 h resulted in reduced cell viability. In addition, LM treatment led to the accumulation of lipid droplets (LDs) in astrocytes, with LD size increasing over prolonged exposure periods. Following 24 h of LM treatment and then 48 h in fresh medium, a significant reduction in intracellular LD size was observed in cultures treated with 5% LM, while no change occurred in cultures exposed to 10% LM. Yet, exposure to 10% LM for 24 h significantly increased the expression of the cholesterol efflux regulatory protein/ATP-binding cassette transporter (ABCA1) gene, responsible for intracellular cholesterol efflux, resulting in reduced cholesterol content within astrocytes. Moreover, LM exposure led to decreased mitochondrial membrane potential (MMP) and increased levels of mature apoptosis-inducing factor (AIF). The smaller LDs were observed to co-localize with microtubule-associated protein 1A/1 B light chain 3 B (LC3) and lysosomal-associated membrane protein-1 (LAMP-1) in LM-treated astrocytes, coinciding with lysosomal acidification. These results indicate that the continuous buildup of LDs in astrocytes residing in lipid-enriched environments may be attributed to disruptions caused by LM in mitochondrial and lysosomal functions. Such disruptions could potentially impede the supportive role of astrocytes in neuronal function.

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暴露于脂质混合物会诱导细胞内脂滴的形成,并损害星形胶质细胞线粒体的功能。
星形胶质细胞是中枢神经系统(CNS)中最主要的胶质细胞,发挥着多种作用,包括为神经元提供代谢支持、提供神经营养因子、促进突触神经递质摄取、调节离子平衡以及参与突触形成。在各种神经系统疾病中都发现了脂质的积累,但星形胶质细胞对富脂质环境的反应仍不清楚。本研究将从新生大鼠皮层中分离出的原代星形胶质细胞暴露于由胆固醇和各种脂肪酸组成的脂质混合物(LM)中,以探究它们的反应。结果表明,5% 或 10% LM 处理 24 小时后,星形胶质细胞的活力保持不变。然而,暴露于 LM 96 小时后,细胞活力会降低。此外,LM 处理会导致脂滴(LDs)在星形胶质细胞中积累,随着暴露时间的延长,LDs 的大小也会增加。经过 24 小时的 LM 处理,然后在新鲜培养基中培养 48 小时后,在用 5% LM 处理的培养物中观察到细胞内 LD 大小显著减少,而暴露于 10% LM 的培养物中则没有变化。然而,暴露于 10%的 LM 24 小时后,负责细胞内胆固醇外流的胆固醇外流调节蛋白/ATP 结合盒转运体(ABCA1)基因的表达明显增加,导致星形胶质细胞内胆固醇含量减少。此外,暴露于 LM 会导致线粒体膜电位(MMP)降低和成熟的凋亡诱导因子(AIF)水平升高。在经 LM 处理的星形胶质细胞中,观察到较小的 LD 与微管相关蛋白 1A/1B 轻链 3B(LC3)和溶酶体相关膜蛋白-1(LAMP-1)共定位,这与溶酶体酸化相吻合。这些结果表明,居住在富脂环境中的星形胶质细胞中 LD 的持续积累可能是由于 LM 破坏了线粒体和溶酶体的功能。这种干扰可能会阻碍星形胶质细胞在神经元功能中发挥支持作用。
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来源期刊
Neurochemistry international
Neurochemistry international 医学-神经科学
CiteScore
8.40
自引率
2.40%
发文量
128
审稿时长
37 days
期刊介绍: Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.
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