Short-Term High-Fat Feeding Does Not Alter Mitochondrial Lipid Respiratory Capacity but Triggers Mitophagy Response in Skeletal Muscle of Mice.
Short-Term High-Fat Feeding Does Not Alter Mitochondrial Lipid Respiratory Capacity but Triggers Mitophagy Response in Skeletal Muscle of Mice.
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短期高脂喂养不会改变小鼠骨骼肌线粒体脂质呼吸能力，但会引发线粒体吞噬反应。
DOI：
10.3389/fendo.2021.651211
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发表时间：
2021
影响因子：
5.2
通讯作者：
Robinson MM
中科院分区：
文献类型：
--
作者：
Ehrlicher SE;Stierwalt HD;Newsom SA;Robinson MM
线粒体的脂质过载与骨骼肌中胰岛素抵抗的发展有关，这可能是肥胖期间2型糖尿病进展的一个促成因素。线粒体通过自噬的定向降解，称为有丝分裂吞噬，有助于线粒体对饮食脂肪变化的适应性反应。我们以前的工作表明，长期(2-4个月)食用高脂肪饮食会增加线粒体脂质氧化能力，但不会改变小鼠吞噬有丝分裂的标志。本研究的目的是研究线粒体对高脂饮食的呼吸适应的初始阶段和线粒体吞噬的激活。C57BL/6J小鼠分别以低脂饮食(LFD，10%脂肪)或高脂饮食(HFD，60%脂肪)喂养3~7天。我们测量了骨骼肌线粒体呼吸和线粒体丰富的部分骨骼肌有丝分裂的蛋白质标记物。在HFD 3天后，与LFD组相比，小鼠的脂质支持的氧化磷酸化程度较低，而电子泄漏较大。7d后，不同饮食组间线粒体呼吸无明显差异。与LFD组相比，HFD组小鼠的自噬小体形成潜能(Beclin-1)和线粒体自噬受体(Bnip3，p62)的激活更强，但下游自噬小体(Lc3II)和溶酶小体(LAMP1)的丰度在3天和7天与LFD组相比没有差异。在培养的肌管中，棕榈酸酯处理降低了线粒体膜电位，过氧化氢处理增加了上游有丝分裂标志物的积累。我们的结论是，几天的高脂肪喂养刺激了骨骼肌有丝分裂的上游激活，可能是通过脂质诱导的氧化应激，而不是下游呼吸的变化。
Lipid overload of the mitochondria is linked to the development of insulin resistance in skeletal muscle which may be a contributing factor to the progression of type 2 diabetes during obesity. The targeted degradation of mitochondria through autophagy, termed mitophagy, contributes to the mitochondrial adaptive response to changes in dietary fat. Our previous work demonstrates long-term (2-4 months) consumption of a high-fat diet increases mitochondrial lipid oxidation capacity but does not alter markers of mitophagy in mice. The purpose of this study was to investigate initial stages of mitochondrial respiratory adaptations to high-fat diet and the activation of mitophagy. C57BL/6J mice consumed either a low-fat diet (LFD, 10% fat) or high-fat diet (HFD, 60% fat) for 3 or 7 days. We measured skeletal muscle mitochondrial respiration and protein markers of mitophagy in a mitochondrial-enriched fraction of skeletal muscle. After 3 days of HFD, mice had lower lipid-supported oxidative phosphorylation alongside greater electron leak compared with the LFD group. After 7 days, there were no differences in mitochondrial respiration between diet groups. HFD mice had greater autophagosome formation potential (Beclin-1) and greater activation of mitochondrial autophagy receptors (Bnip3, p62) in isolated mitochondria, but no difference in downstream autophagosome (LC3II) or lysosome (Lamp1) abundance after both 3 and 7 days compared with the LFD groups. In cultured myotubes, palmitate treatment decreased mitochondrial membrane potential and hydrogen peroxide treatment increased accumulation of upstream mitophagy markers. We conclude that several days of high-fat feeding stimulated upstream activation of skeletal muscle mitophagy, potentially through lipid-induced oxidative stress, without downstream changes in respiration.
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影响因子：
9.8
作者：
Choi, Jin Woo;Ohn, Jung Hun;Park, Kyong Soo
通讯作者：
Park, Kyong Soo
影响因子：
5.5
作者：
Nichenko, Anna S.;Southern, W. Michael;Call, Jarrod A.
通讯作者：
Call, Jarrod A.
影响因子：
15.9
作者：
Anderson, Ethan J.;Lustig, Mary E.;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell
DOI：
10.1249/mss.0b013e31822b0bd4
发表时间：
2012-02-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Daussin, Frederic N.;Rasseneur, Laurence;Richard, Ruddy
通讯作者：
Richard, Ruddy
影响因子：
7.7
作者：
Novak, Ivana;Kirkin, Vladimir;Dikic, Ivan
通讯作者：
Dikic, Ivan