Improved Hepatic Lipid Composition Following Short-Term Exercise in Nonalcoholic Fatty Liver Disease

Increased hepatocyte apoptosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and contributes to the profibrogenic state responsible for the progression to nonalcoholic steatohepatitis (NASH). Strategies aimed at reducing apoptosis may result in better outcomes for individuals with NAFLD. We therefore examined the effect of a short-term exercise program on markers of apoptosis—plasma cytokeratin 18 (CK18) fragments, alanine aminotransferase (ALT), aspartate aminotransferase (AST), soluble Fas (sFas), and sFas ligand (sFasL)—in 13 obese individuals with NAFLD [body mass index 35.2 ± 1.2 kg/m2, >5% intrahepatic lipid (IHL) assessed by 1H-MR spectroscopy]. Exercise consisted of treadmill walking for 60 min/day on 7 consecutive days at ∼85% of maximal heart rate. Additionally, subjects underwent an oral glucose tolerance test and a maximal oxygen consumption (V̇o2max) test before and after the exercise intervention. The Matsuda index was used to assess insulin sensitivity. We observed significant decreases in CK18 fragments (558.4 ± 106.8 vs. 323.4 ± 72.5 U/l, P < 0.01) and ALT (30.2 ± 5.1 vs. 24.3 ± 4.8 U/l, P < 0.05), and an increase in whole body fat oxidation (49.3 ± 6.1 vs. 69.4 ± 7.1 mg/min, P < 0.05), while decreases in circulating sFasL approached statistical significance (66.5 ± 6.0 vs. 63.0 ± 5.7 pg/ml, P = 0.06), as did the relationship between percent change in circulating CK18 fragments and ALT (r = 0.55, P = 0.05). We also observed a significant correlation between changes in fat oxidation and circulating sFasL (rho = −0.65, P < 0.05). There was no change in IHL following the intervention (18.2 ± 2.5 vs. 17.5 ± 2.1%, NS). We conclude that short-term exercise reduces a circulatory marker of hepatocyte apoptosis in obese individuals with NAFLD and propose that changes in the proapoptotic environment may be mediated through improved insulin sensitivity and increased oxidative capacity.

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LncRNA NEAT1 promotes hepatic lipid accumulation via regulating miR-146a-5p/ROCK1 in nonalcoholic fatty liver disease

Life Sciences ◽

10.1016/j.lfs.2019.116829 ◽

2019 ◽

Vol 235 ◽

pp. 116829 ◽

Cited By ~ 6

Author(s):

Xi Chen ◽

Xin-Rui Tan ◽

Shi-Jun Li ◽

Xing-Xing Zhang

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Lipid Accumulation ◽

Fatty Liver Disease ◽

Nonalcoholic Fatty Liver ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation ◽

Lncrna Neat1

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Understanding the Role of Exercise in Nonalcoholic Fatty Liver Disease: ERS-Linked Molecular Pathways

Mediators of Inflammation ◽

10.1155/2020/6412916 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Yong Zou ◽

Zhengtang Qi

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Lipid Accumulation ◽

Fatty Liver Disease ◽

Molecular Pathways ◽

Nonalcoholic Fatty Liver ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation

Nonalcoholic fatty liver disease (NAFLD) is globally prevalent and characterized by abnormal lipid accumulation in the liver, frequently accompanied by insulin resistance (IR), enhanced hepatic inflammation, and apoptosis. Recent studies showed that endoplasmic reticulum stress (ERS) at the subcellular level underlies these featured pathologies in the development of NAFLD. As an effective treatment, exercise significantly reduces hepatic lipid accumulation and thus alleviates NAFLD. Confusingly, these benefits of exercise are associated with increased or decreased ERS in the liver. Further, the interaction between diet, medication, exercise types, and intensity in ERS regulation is more confusing, though most studies have confirmed the benefits of exercise. In this review, we focus on understanding the role of exercise-modulated ERS in NAFLD and ERS-linked molecular pathways. Moderate ERS is an essential signaling for hepatic lipid homeostasis. Higher ERS may lead to increased inflammation and apoptosis in the liver, while lower ERS may lead to the accumulation of misfolded proteins. Therefore, exercise acts like an igniter or extinguisher to keep ERS at an appropriate level by turning it up or down, which depends on diet, medications, exercise intensity, etc. Exercise not only enhances hepatic tolerance to ERS but also prevents the malignant development of steatosis due to excessive ERS.

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In vivo1H-MRS hepatic lipid profiling in nonalcoholic fatty liver disease: An animal study at 9.4 T

Magnetic Resonance in Medicine ◽

10.1002/mrm.24510 ◽

2012 ◽

Vol 70 (3) ◽

pp. 620-629 ◽

Cited By ~ 11

Author(s):

Yunjung Lee ◽

Hee-Jung Jee ◽

Hyungjoon Noh ◽

Geun-Hyung Kang ◽

Juyeun Park ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Animal Study ◽

Fatty Liver Disease ◽

Lipid Profiling ◽

Nonalcoholic Fatty Liver ◽

Hepatic Lipid

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Increased Diacylglycerols Characterize Hepatic Lipid Changes in Progression of Human Nonalcoholic Fatty Liver Disease; Comparison to a Murine Model

PLoS ONE ◽

10.1371/journal.pone.0022775 ◽

2011 ◽

Vol 6 (8) ◽

pp. e22775 ◽

Cited By ~ 79

Author(s):

D. Lee Gorden ◽

Pavlina T. Ivanova ◽

David S. Myers ◽

J. Oliver McIntyre ◽

Michael N. VanSaun ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Murine Model ◽

Fatty Liver Disease ◽

Nonalcoholic Fatty Liver ◽

Hepatic Lipid

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Escherichia fergusonii promotes nonobese nonalcoholic fatty liver disease by interfering with host hepatic lipid metabolism through its own msRNA 23487

Cellular and Molecular Gastroenterology and Hepatology ◽

10.1016/j.jcmgh.2021.12.003 ◽

2021 ◽

Author(s):

Feng-Zhi Xin ◽

Ze-Hua Zhao ◽

Xiao-Lin Liu ◽

Qin Pan ◽

Zi-Xuan Wang ◽

...

Keyword(s):

Lipid Metabolism ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Hepatic Lipid Metabolism ◽

Nonalcoholic Fatty Liver ◽

Hepatic Lipid

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Pharmacological management of nonalcoholic fatty liver disease: Limitations, challenges and new therapeutic opportunities

Journal of Atherosclerosis Prevention and Treatment ◽

10.53590/japt.02.1001 ◽

2019 ◽

pp. 28-37

Author(s):

Eleni A. Karavia ◽

Kyriakos E. Kypreos

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Hepatic Steatosis ◽

Fatty Liver Disease ◽

Lifestyle Changes ◽

Pharmacological Management ◽

Nonalcoholic Fatty Liver ◽

Hepatic Lipid ◽

Stress Changes

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of metabolic disorders ranging from a simple accumulation of excess triglycerides in the liver (hepatic steatosis) to hepatic steatosis with inflammation, fibrosis, and cirrhosis (steatohepatitis or non-alcoholic steatohepatitis (NASH)). Studies in humans and animal models suggested that alterations in hepatic lipid metabolism, increased generation of reactive oxygen species and consequently oxidative stress, changes in mitochondrial function, DNA damage, microbial infections and release of various cytokines may contribute to the pathogenesis of NAFLD and its progression to NASH. Recent data also suggest an important role of the lipoprotein transport system in hepatic lipid deposition. Currently, no drugs are approved for the treatment of NAFLD and NASH and existing pharmacotherapy aims at the management of intercurrent diseases such as obesity, hyperlipidemia, insulin resistance, and type 2 diabetes mellitus. All guidelines acknowledge that any medicines prescribed for NAFLD treatment should be considered as an off-label treatment and that their efficacy and safety should be carefully monitored. Although current pharmacotherapy may seem limited and of questionable efficacy, there is optimism that innovative safe and effective options for the management of the disease will be made available shortly since specialized drugs such as obeticholic acid, elafibranor and cenicriviroc, are presently tested in clinical trials. Given that patients with NAFLD without steatohepatitis or fibrosis have excellent prognosis if they adopt appropriate therapeutic lifestyle changes, it is generally accepted that pharmacological treatments should be limited to those with established NASH and fibrosis while subjects with early manifestations of NAFLD should resort to therapeutic lifestyle and nutritional changes.

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