Exercise-Induced Autophagy in Fatty Liver Disease

Chun, Sung Kook; Lee, Sooyeon; Yang, Ming Jim; Leeuwenburgh, Christiaan; Kim, Jae-Sung

doi:10.1249/jes.0000000000000116

Cited by 27 publications

(25 citation statements)

References 51 publications

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“…In this study, we found that MAP1LC3A a marker of lipophagy, lipid specific autophagy, is dramatically downregulated in over-nutrition induced NAFLD liquid crystal hepatic lipid droplet accumulation. As exercise can improve lipid over accumulation by increasing lipophagy [49,50], the next step is to investigate whether exercise can reactivate MAP1LC3A associated autophagy. Understanding the relationship between liquid crystal hepatic lipid droplets and the MAP1LC3A autophagy could provide a unique prospective towards understanding, preventing, and treating NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Nonalcoholic fatty liver disease experiences accumulation of hepatic liquid crystal associated with increasing lipophagy

Wang

Jones

et al. 2020

Cell Biosci

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Background: In the past 30 years, incidences of non-alcoholic fatty liver disease (NAFLD) has risen by 30%. However, there is still no clear mechanism or accurate method of anticipating liver failure. Here we reveal the phase transitions of liquid crystalline qualities in hepatic lipid droplets (HLDs) as a novel method of anticipating prognosis. Methods: NAFLD was induced by feeding C57BL/6J mice on a high-fat (HiF) diet. These NAFLD livers were then evaluated under polarized microscopy, X-ray diffraction and small-angle scattering, lipid component chromatography analysis and protein expression analysis. Optically active HLDs from mouse model and patient samples were both then confirmed to have liquid crystal characteristics. Liver MAP1LC3A expression was then evaluated to determine the role of autophagy in liquid crystal HLD (LC-HLD) formation. Results: Unlike the normal diet cohort, HiF diet mice developed NAFLD livers containing HLDs exhibiting Maltese cross birefringence, phase transition, and fluidity signature to liquid crystals. These LC-HLDs transitioned to anisotropic crystal at 0 °C and remain crystalline. Temperature increase to 42 °C causes both liquid crystal and crystal HLDs to convert to isotropic droplet form. These isotropic HLDs successfully transition to anisotropic LC with fast temperature decrease and anisotropic crystal with slow temperature decrease. These findings were duplicated in patient liver. Patient LC-HLDs with no inner optical activity were discovered, hinting at lipid saturation as the mechanism through which HLD acquire LC characteristics. Downregulation of MAP1LC3A in conjunction with increased LC-HLD also implicated autophagy in NAFLD LC-HLD formation. Conclusions: Increasing concentrations of amphiphilic lipids in HLDs favors organization into alternating hydrophilic and hydrophobic layers, which present as LC-HLDs. Thus, evaluating the extent of liquid crystallization with phase transition in HLDs of NAFLD patients may reveal disease severity and predict impending liver damage.

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Section: Discussionmentioning

confidence: 99%

Nonalcoholic fatty liver disease experiences accumulation of hepatic liquid crystal associated with increasing lipophagy

Wang

Jones

et al. 2020

Cell Biosci

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“…Autophagy is also used by H. pylori to survive 78,79 CD Defect/ active MAP1S, NOD2, CLEC12A, ATG16L, NDP52, IRGM NOD2 direct ATG16L1 on the plasma membrane and initiate autophagy. Onset of CD is triggered by dysfunction of autophagy [80][81][82] Fatty liver disease Defect SREBP-2, PNPLA8, FGF21 Impairment of autophagy decreases insulin resistance and enhances oxidative stress and deteriorates hepatocyte damage [83][84][85] Alcoholic liver disease Defect CNR2, ATG5…”

Section: Becn1 Cftrmentioning

confidence: 99%

Modulation of autophagy in human diseases strategies to foster strengths and circumvent weaknesses

Sui

Zhang

et al. 2019

Medicinal Research Reviews

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Autophagy is central to the maintenance of intracellular homeostasis across species. Accordingly, autophagy disorders are linked to a variety of diseases from the embryonic stage until death, and the role of autophagy as a therapeutic target has been widely recognized. However, autophagy‐associated therapy for human diseases is still in its infancy and is supported by limited evidence. In this review, we summarize the landscape of autophagy‐associated diseases and current autophagy modulators. Furthermore, we investigate the existing autophagy‐associated clinical trials, analyze the obstacles that limit their progress, offer tactics that may allow barriers to be overcome along the way and then discuss the therapeutic potential of autophagy modulators in clinical applications.

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“…In the accompanying review by Chun et al (4), the mechanisms by which exercise benefits NAFLD has focused primarily on autophagy. Extensive preclinical and consistent but very limited data in patients with NAFL suggest impaired hepatic autophagy in NAFLD.…”

mentioning

confidence: 99%

“…Exercise is an effective non-pharmacological intervention that promotes improvement of liver function tests in NAFLD and in the accompanying article, the thesis is that exercise is beneficial through enhanced autophagy in the skeletal muscle and possibly liver. The mechanisms by which exercise stimulates hepatic autophagy are currently areas of active investigation as mentioned in the article by Chun et al (4). There is emerging evidence that exercise induced secretion of irisin and potentially other myokines promote browning of fat and may have direct effects on hepatocyte triglyceride accumulation (4).…”

mentioning

confidence: 99%

“…The mechanisms by which exercise stimulates hepatic autophagy are currently areas of active investigation as mentioned in the article by Chun et al (4). There is emerging evidence that exercise induced secretion of irisin and potentially other myokines promote browning of fat and may have direct effects on hepatocyte triglyceride accumulation (4). However, the beneficial effects of exercise cannot be ascribed only to stimulation of autophagy.…”

mentioning

confidence: 99%

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Are Exercise Benefits in Nonalcoholic Fatty Liver Disease Due to Increased Autophagy?

Dasarathy

2017

Exercise and Sport Sciences Reviews

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Exercise-Induced Autophagy in Fatty Liver Disease

Cited by 27 publications

References 51 publications

Nonalcoholic fatty liver disease experiences accumulation of hepatic liquid crystal associated with increasing lipophagy

Nonalcoholic fatty liver disease experiences accumulation of hepatic liquid crystal associated with increasing lipophagy

Modulation of autophagy in human diseases strategies to foster strengths and circumvent weaknesses

Are Exercise Benefits in Nonalcoholic Fatty Liver Disease Due to Increased Autophagy?

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