Differential Effects of Oleic and Palmitic Acids on Lipid Droplet-Mitochondria Interaction in the Hepatic Cell Line HepG2.
Differential Effects of Oleic and Palmitic Acids on Lipid Droplet-Mitochondria Interaction in the Hepatic Cell Line HepG2.
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DOI：
10.3389/fnut.2021.775382
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发表时间：
2021
影响因子：
5
通讯作者：
Troncoso R
中科院分区：
文献类型：
--
作者：
Eynaudi A;Díaz-Castro F;Bórquez JC;Bravo-Sagua R;Parra V;Troncoso R
脂肪酸超载，无论是饱和棕榈酸（PA）还是不饱和油酸（OA），都会导致甘油三酯积聚到称为脂滴（LD）的专门细胞器中。然而，只有PA超载导致由线粒体功能障碍介导的肝损伤。这些不同的结果是否源于PA和OA对LD和线粒体关节动力学的不同影响尚不清楚。在这里，我们对比了两种脂肪酸如何影响HepG2细胞中细胞器和线粒体生物能量学之间的形态和相互作用。通过共聚焦显微镜，我们发现短期（2-24 h） OA过载比PA更能促进LD积累。氧极谱显示两种处理均刺激线粒体呼吸；然而，OA有利于线粒体电位的全面建立，而PA诱发线粒体断裂，并伴有atp导向的代谢。尽管与OA相比，pa诱导的LD-线粒体接近性增加较少，但与高活性线粒体相关的LD表明，它们主要相互作用为脂肪酸氧化和ATP合成提供燃料（即代谢“活性”LD）。相反，OA过载似乎刺激LD-线粒体相互作用，主要是为了LD生长（因此代谢“被动”LD）。总之，这些差异表明OA很容易在LD中积累，可能会降低其毒性，而PA更容易刺激线粒体氧化代谢，这可能有助于肝损伤的进展。
Fatty acid overload, either of the saturated palmitic acid (PA) or the unsaturated oleic acid (OA), causes triglyceride accumulation into specialized organelles termed lipid droplets (LD). However, only PA overload leads to liver damage mediated by mitochondrial dysfunction. Whether these divergent outcomes stem from differential effects of PA and OA on LD and mitochondria joint dynamics remains to be uncovered. Here, we contrast how both fatty acids impact the morphology and interaction between both organelles and mitochondrial bioenergetics in HepG2 cells. Using confocal microscopy, we showed that short-term (2–24 h) OA overload promotes more and bigger LD accumulation than PA. Oxygen polarography indicated that both treatments stimulated mitochondrial respiration; however, OA favored an overall build-up of the mitochondrial potential, and PA evoked mitochondrial fragmentation, concomitant with an ATP-oriented metabolism. Even though PA-induced a lesser increase in LD-mitochondria proximity than OA, those LD associated with highly active mitochondria suggest that they interact mainly to fuel fatty acid oxidation and ATP synthesis (that is, metabolically “active” LD). On the contrary, OA overload seemingly stimulated LD-mitochondria interaction mainly for LD growth (thus metabolically “passive” LDs). In sum, these differences point out that OA readily accumulates in LD, likely reducing their toxicity, while PA preferably stimulates mitochondrial oxidative metabolism, which may contribute to liver damage progression.
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影响因子：
4.6
作者：
Bravo-Sagua R;López-Crisosto C;Parra V;Rodriguez-Peña M;Rothermel BA;Quest AF;Lavandero S
通讯作者：
Lavandero S
影响因子：
4
作者：
Aon MA;Bhatt N;Cortassa SC
通讯作者：
Cortassa SC
影响因子：
21.3
作者：
Eisner V;Picard M;Hajnóczky G
通讯作者：
Hajnóczky G
影响因子：
7.7
作者：
Cnop, M;Hannaert, JC;Pipeleers, DG
通讯作者：
Pipeleers, DG
DOI：
10.15252/embj.201694914
发表时间：
2017-06-01
期刊：
The EMBO journal
影响因子：
--
作者：
Boutant M;Kulkarni SS;Joffraud M;Ratajczak J;Valera-Alberni M;Combe R;Zorzano A;Cantó C
通讯作者：
Cantó C