Gene expression signature of exercise and change of diet on non-alcoholic fatty liver disease in mice

2021 ◽  
pp. 1-12
Author(s):  
L. Melo ◽  
A. Hagar ◽  
J.E. Klaunig
Keyword(s):  
Immune Response ◽  
Fatty Liver ◽  
Aerobic Exercise ◽  
Molecular Mechanisms ◽  
Exercise Intervention ◽  
Gene Expression Signature ◽  
Sequencing Analysis ◽  
Alcoholic Fatty Liver ◽  
Exercise Interventions ◽  
Expression Signature

Non-alcoholic fatty liver diseases (NAFLD) are particularly prevalent in the general Western adult population, with around one third of the population suffering from the disease. Evidence shows that NAFLD is associated with metabolic syndromes such as obesity, insulin resistance, and hypertension. Currently, the sole therapy for NAFLD involves exercise intervention. Studies showed that, with and without weight loss, exercise interventions produced a significant cutback in intrahepatic lipid content in humans, but better controlled studies that can investigate the cellular and molecular mechanisms are still lacking. In the current study we perform RNA sequencing analysis on liver samples from C57BL/6 mice submitted to aerobic exercise and diet interventions that are human-translatable and determine the genetic expression signature of exercise in the NAFLD onset. We show that aerobic exercise affects genes and pathways related to liver metabolism, muscle contraction and relaxation, immune response and inflammation, and development of liver cancer, counteracting non-alcoholic steatohepatitis and hepatocellular carcinoma development. While genes and pathways implicating immune response are activated by aerobic exercise in all interventions, the most effective intervention in terms of improvement of NASH is the combination of aerobic exercise with change of diet.

scholarly journals Aerobic exercise improves hippocampal blood flow for hypertensive Apolipoprotein E4 carriers

2021 ◽  
pp. 0271678X2199034
Author(s):  
Carolyn S Kaufman ◽  
Robyn A Honea ◽  
Joseph Pleen ◽  
Rebecca J Lepping ◽  
Amber Watts ◽  
...  
Keyword(s):  
Blood Flow ◽  
Aerobic Exercise ◽  
Genetic Risk ◽  
Exercise Intervention ◽  
Late Onset ◽  
Control Group ◽  
Carrier Status ◽  
Or Education ◽  
Exercise Interventions ◽  
Apolipoprotein E4

Cerebrovascular dysfunction likely contributes causally to Alzheimer’s disease (AD). The strongest genetic risk factor for late-onset AD, Apolipoprotein E4 ( APOE4), may act synergistically with vascular risk to cause dementia. Therefore, interventions that improve vascular health, such as exercise, may be particularly beneficial for APOE4 carriers. We assigned cognitively normal adults (65–87 years) to an aerobic exercise intervention or education only. Arterial spin labeling MRI measured hippocampal blood flow (HBF) before and after the 52-week intervention. We selected participants with hypertension at enrollment (n = 44). For APOE4 carriers, change in HBF (ΔHBF) was significantly ( p = 0.006) higher for participants in the exercise intervention (4.09 mL/100g/min) than the control group (−2.08 mL/100g/min). There was no difference in ΔHBF between the control (−0.32 mL/100g/min) and exercise (−0.54 mL/100g/min) groups for non-carriers (p = 0.918). Additionally, a multiple regression showed an interaction between change in systolic blood pressure (ΔSBP) and APOE4 carrier status on ΔHBF ( p = 0.035), with reductions in SBP increasing HBF for APOE4 carriers only. Aerobic exercise improved HBF for hypertensive APOE4 carriers only. Additionally, only APOE4 carriers exhibited an inverse relationship between ΔSBP and ΔHBF. This suggests exercise interventions, particularly those that lower SBP, may be beneficial for individuals at highest genetic risk of AD. ClinicalTrials.gov Identifier: NCT02000583

Molecular mechanisms of non-alcoholic fatty liver disease development

2021 ◽  
Vol 24 (4) ◽  
pp. 120
Author(s):  
T.S. Sall ◽  
E.S. Shcherbakova ◽  
S.I. Sitkin ◽  
T.Ya. Vakhitov ◽  
I.G. Bakulin ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Disease Development ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals PO-103 The mechanism of long-term regular exercise intervention on liver injury in patients with NAFLD based on miR-146a regulation of TLR4/NF-KB signaling pathway

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Qi Peng ◽  
Jiaqin Chen ◽  
Wei Chen ◽  
Chang Feng Shao ◽  
Afang Yuan
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Exercise Intervention ◽  
Exercise Group ◽  
Control Group ◽  
Regular Exercise ◽  
Alcoholic Fatty Liver

Objective To investigate the effects of long-term regular exercise on hepatic function in patients with non-alcoholic fatty liver (NAFLD) using blood biochemistry and liver fibrosis markers, and to compare the differential expression of cytokines related to TLR4/NF-KB signaling pathway. A preliminary discussion was made on its regulation mechanism. Methods Forty patients with NAFLD diagnosed in the Hunan Normal University School of Medicine, according to the degree of steatosis and exercise intervention, the patients were divided into control group (NAFLD group) 20 cases and long-term regular exercise group 20 cases, and the same time in our hospital Twenty patients with physical examination were normal controls; general data of all subjects, ALT, AST, GGT, serum type III procollagen (PCIII), hyaluronan (HA), and type IV collagen (CIV) were examined; Fluorescent quantitative PCR was used to detect the differential expression of TLR4/NF-KB signaling pathway-related cytokines and miR-146a in the blood of each group of subjects, revealing the effects and possible mechanisms of long-term regular exercise on liver fibrosis. Results Compared with the normal group, the levels of serum ALT, AST, GGT, PCIII, HA, and CIV in the non-alcoholic fatty liver patients were significantly lower in the long-term regular exercise group than in the control group; blood TLR4, NF-KB, MY-D88 Compared with the control group, the gene expression level was significantly downregulated in the long-term regular exercise group.  Conclusions Long-term regular exercise can effectively reduce nonalcoholic inflammatory liver injury and has a clear anti-fibrotic effect. Its mechanism may be related to long-term regular exercise through regulating the TLR4/NF-KB signaling pathway related factors and the regulation of molecular miR-146a, reducing inflammation and preventing the formation of fibrosis.

Is liver fat detrimental to vessels?: intersections in the pathogenesis of NAFLD and atherosclerosis

2008 ◽  
Vol 115 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Paola Loria ◽  
Amedeo Lonardo ◽  
Giovanni Targher
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Liver Fat ◽  
Cvd Risk ◽  
Alcoholic Fatty Liver ◽  
Insulin Resistant ◽  
Major Player

NAFLD (non-alcoholic fatty liver disease) encompasses the spectrum of fatty liver disease in insulin-resistant individuals who often display T2DM (Type 2 diabetes mellitus) and obesity. The present review highlights the pathophysiological basis and clinical evidence for a possible causal linkage between NAFLD and CVD (cardiovascular disease). The role of traditional and non-traditional CVD risk factors in the pathophysiology of NAFLD is considered in the first part of the review, with the basic science shared by atherogenesis and hepatic steatogenesis discussed in depth in the second part. In conclusion, NAFLD is not an innocent bystander, but a major player in the development and progression of CVD. NAFLD and CVD also share similar molecular mechanisms and targeted treatment strategies. On the research side, studies should focus on interventions aimed at restoring energy homoeostasis in lipotoxic tissues and at improving hepatic (micro)vascular blood supply.

scholarly journals A Role for Gut Microbiome Fermentative Pathways in Fatty Liver Disease Progression

2020 ◽  
Vol 9 (5) ◽  
pp. 1369 ◽  
Author(s):  
Paula Iruzubieta ◽  
Juan M. Medina ◽  
Raúl Fernández-López ◽  
Javier Crespo ◽  
Fernando de la Cruz
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Disease Progression ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Alcohol Fermentation ◽  
Alcoholic Fatty Liver ◽  
Liver Disease Progression ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alcohol-fermentation pathways in the GM may outcompete healthier, acid-producing members of the microbiota. In this way, GM ecology may precipitate a self-sustaining vicious cycle, boosting liver disease progression.

scholarly journals A Systematic Review of the Effects of Exercise on Hormones in Women with Polycystic Ovary Syndrome

2020 ◽  
Vol 5 (2) ◽  
pp. 35
Author(s):  
Grei Shele ◽  
Jessica Genkil ◽  
Diana Speelman
Keyword(s):  
Systematic Review ◽  
Polycystic Ovary Syndrome ◽  
Aerobic Exercise ◽  
Exercise Intervention ◽  
Polycystic Ovary ◽  
Healthy Weight ◽  
Ovary Syndrome ◽  
Exercise Interventions ◽  
The Impact ◽  
Androgen Levels

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is characterized by menstrual irregularity and elevated serum androgens, and is often accompanied by insulin resistance. The etiology of PCOS is unknown. Lifestyle interventions and weight loss, where appropriate, remain first-line treatments for women with PCOS. Regular physical activity is recommended for women with PCOS to maintain a healthy weight and cardiovascular fitness. Purpose: To review the evidence for the impact of various exercise interventions on hormone levels in women with PCOS. Methods: A systematic review of original studies indexed in PubMed that utilized an exercise intervention in women with PCOS and reported hormone values pre- and post-intervention. Studies in which the effects of the exercise intervention could be determined were included. Results: Vigorous aerobic exercise improves insulin measures in women with PCOS. Resistance or strength training may improve androgen levels, though additional studies are warranted. Studies with yoga are limited but suggest improvements in androgens. Limited information is available on the impact of exercise on adipokines and anti-Müllerian hormone, warranting further investigation. Conclusions: Recommended guidelines for women with PCOS include vigorous aerobic exercise and resistance training to improve measures of insulin sensitivity and androgen levels.

scholarly journals Genome-wide analysis identified proteins associated with mitochondrial function and inflammation activation crucially regulating the pathogenesis of fatty liver disease

2021 ◽  
Author(s):  
Letian Zhang ◽  
Tingjun Liu ◽  
Chengzhang Hu ◽  
Xuan Zhang ◽  
Qin Zhang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Biological Processes ◽  
Human Beings ◽  
Alcoholic Fatty Liver ◽  
Therapeutic Drugs ◽  
Genome Wide ◽  
Performance Results

Abstract Background Fatty liver disease prevalently occurs in commercial postpartum dairies, resulting in a worldwide high culling rate because of their subsequent limitations of production and reproduction performance. Results Fatty liver-specific proteome and acetylome analysis revealed that energy metabolism suppression closely associated with mitochondrial dysfunction and inflammation activation are shown to be remarkable biological processes underlying the development of fatty liver disease, thereby acetylation modification of proteins modulating these processes. Twenty pivotal genetic factors/genes that differentially expressing and being acetylation modified in liver were identified and proposed to regulate the pathogenesis of fatty liver dairies. These proteins were confirmed to be differentially expressing in individual liver tissues, eight of which being validated through immunohistochemistry assay. Conclusion This study provided a comprehensive proteome and acetylome profile of fatty liver of dairy cows, and revealed potential important biological processes and essential regulators in the pathogenesis of fatty liver disease. Expectantly, understanding the molecular mechanisms of the pathogenesis of fatty liver disease in dairies, as an animal model of non-alcoholic fatty liver disease (NAFLD) in human beings, which is a clinico-pathologically defined process associated with metabolic syndrome, could inspire and facilitate the development of efficacious therapeutic drugs on NAFLD.

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