Chemokines in Non-alcoholic Fatty Liver Disease: A Systematic Review and Network Meta-Analysis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background: Previous results on the relationship between non-alcoholic fatty liver disease (NAFLD) and chemokine concentrations were inconsistent. The purpose of this network meta-analysis was to evaluate the link between chemokine system and NAFLD.

Methods: Relevant data, published not later than June 31, 2019, were searched in the databases of PubMed, Embase, Cochrane Library, and Web of Science. A network meta-analysis was used to rank the chemokines by surface under the cumulative ranking (SUCRA) probabilities. In addition, standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated as group differences in the chemokine concentrations.

Results: The search in the databases identified 46 relevant studies that investigated the relationship between 15 different chemokines and NAFLD using 4,753 patients and 4,059 controls. Results from the network meta-analysis showed that the concentrations of CCL2 and CXCL8 in the non-alcoholic fatty liver (NAFL) group was significantly higher than that in the control group (SMDs of 1.51 and 1.95, respectively), and the concentrations of CCL3, CCL4, CCL20, CXCL8, and CXCL10 in the non-alcoholic steatohepatitis (NASH) group was significantly higher than that in the control group (SMDs of 0.90, 2.05, 2.16, 0.91, and 1.46, respectively). SUCRA probabilities showed that CXCL8 had the highest rank in NAFL for all chemokines and CCL20 had the highest rank in NASH for all chemokines.

Conclusion: Elevated concentrations of CCL2, CCL4, CCL20, CXCL8, and CXCL10 may be associated with NAFL or NASH. In this regard, more population-based studies are needed to ascertain this hypothesis.

Systematic Review Registration: PROSPERO: CRD42020139373.

Related collections

Most cited references 34

Record: found
Abstract: not found
Article: not found

Past, present and future perspectives in nonalcoholic fatty liver disease

Arun Sanyal (2019)

0 comments Cited 200 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity.

Fredy Saudale, Bart Staels, Caroline Duval … (2010)

Kupffer cells have been implicated in the pathogenesis of various liver diseases. However, their involvement in metabolic disorders of the liver, including fatty liver disease, remains unclear. The present study sought to determine the impact of Kupffer cells on hepatic triglyceride storage and to explore the possible mechanisms involved. To that end, C57Bl/6 mice rendered obese and steatotic by chronic high-fat feeding were treated for 1 week with clodronate liposomes, which cause depletion of Kupffer cells. Loss of expression of marker genes Cd68, F4/80, and Clec4f, and loss of Cd68 immunostaining verified almost complete removal of Kupffer cells from the liver. Also, expression of complement components C1, the chemokine (C-C motif) ligand 6 (Ccl6), and cytokines interleukin-15 (IL-15) and IL-1beta were markedly reduced. Importantly, Kupffer cell depletion significantly decreased liver triglyceride and glucosylceramide levels concurrent with increased expression of genes involved in fatty acid oxidation including peroxisome proliferator-activated receptor alpha (PPARalpha), carnitine palmitoyltransferase 1A (Cpt1alpha), and fatty acid transport protein 2 (Fatp2). Treatment of mice with IL-1beta decreased expression of PPARalpha and its target genes, which was confirmed in primary hepatocytes. Consistent with these data, IL-1beta suppressed human and mouse PPARalpha promoter activity. Suppression of PPARalpha promoter activity was recapitulated by overexpression of nuclear factor kappaB (NF-kappaB) subunit p50 and p65, and was abolished upon deletion of putative NF-kappaB binding sites. Finally, IL-1beta and NF-kappaB interfered with the ability of PPARalpha to activate gene transcription. Our data point toward important cross-talk between Kupffer cells and hepatocytes in the regulation of hepatic triglyceride storage. The effect of Kupffer cells on liver triglycerides are at least partially mediated by IL-1beta, which suppresses PPARalpha expression and activity.

0 comments Cited 165 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

C-C Chemokine Receptor 2 (CCR2) Regulates the Hepatic Recruitment of Myeloid Cells That Promote Obesity-Induced Hepatic Steatosis

Amrom Obstfeld, Eiji Sugaru, Marie Thearle … (2010)

OBJECTIVE Obesity induces a program of systemic inflammation that is implicated in the development of many of its clinical sequelae. Hepatic inflammation is a feature of obesity-induced liver disease, and our previous studies demonstrated reduced hepatic steatosis in obese mice deficient in the C-C chemokine receptor 2 (CCR2) that regulates myeloid cell recruitment. This suggests that a myeloid cell population is recruited to the liver in obesity and contributes to nonalcoholic fatty liver disease. RESEARCH DESIGN AND METHODS We used fluorescence-activated cell sorting to measure hepatic leukocyte populations in genetic and diet forms of murine obesity. We characterized in vivo models that increase and decrease an obesity-regulated CCR2-expressing population of hepatic leukocytes. Finally, using an in vitro co-culture system, we measured the ability of these cells to modulate a hepatocyte program of lipid metabolism. RESULTS We demonstrate that obesity activates hepatocyte expression of C-C chemokine ligand 2 (CCL2/MCP-1) leading to hepatic recruitment of CCR2+ myeloid cells that promote hepatosteatosis. The quantity of these cells correlates with body mass and in obese mice represents the second largest immune cell population in the liver. Hepatic expression of CCL2 increases their recruitment and in the presence of dietary fat induces hepatosteatosis. These cells activate hepatic transcription of genes responsible for fatty acid esterification and steatosis. CONCLUSIONS Obesity induces hepatic recruitment of a myeloid cell population that promotes hepatocyte lipid storage. These findings demonstrate that recruitment of myeloid cells to metabolic tissues is a common feature of obesity, not limited to adipose tissue.

0 comments Cited 123 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Xiongfeng Pan: URI : http://loop.frontiersin.org/people/575393/overview

Shi Wu Wen: URI : http://loop.frontiersin.org/people/977134/overview

Journal

Journal ID (nlm-ta): Front Immunol

Journal ID (publisher-id): Front. Immunol.

Title: Frontiers in Immunology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-3224

Publication date (Electronic): 18 September 2020

Publication date Collection: 2020

Volume: 11

Electronic Location Identifier: 1802

Affiliations

[1] ¹Xiangya School of Public Health, Central South University , Changsha, China

[2] ²Department of Mathematics and Statistics, Mzuzu University , Mzuzu, Malawi

[3] ³Department of Obstetrics and Gynaecology, University of Ottawa , Ottawa, ON, Canada

[4] ⁴Ottawa Hospital Research Institute , Ottawa, ON, Canada

[5] ⁵Department of Food Science and Biotechnol, Kagoshima University , Kagoshima, Japan

Author notes

Edited by: Bodduluri Haribabu, University of Louisville, United States

Reviewed by: Jose Miguel Rodriguez Frade, Consejo Superior de Investigaciones Científicas (CSIC), Spain; Remo Castro Russo, Federal University of Minas Gerais, Brazil

*Correspondence: Jiayou Luo jiayouluo@ 123456126.com

This article was submitted to Cytokines and Soluble Mediators in Immunity, a section of the journal Frontiers in Immunology

Article

DOI: 10.3389/fimmu.2020.01802

PMC ID: 7530185

PubMed ID: 33042108

SO-VID: f454ec3a-c1e2-48b0-8e32-32fa6b19bf71

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 26 March 2020

Date accepted : 06 July 2020

Page count

Figures: 3, Tables: 2, Equations: 0, References: 51, Pages: 11, Words: 6874

Comments

Comment on this article

scite_

Cited by 31

See all cited by

Most referenced authors 1,122

See all reference authors

Chemokines in Non-alcoholic Fatty Liver Disease: A Systematic Review and Network Meta-Analysis

Read this article at

Abstract

Related collections

Gamma Delta T cells

Most cited references 34

Past, present and future perspectives in nonalcoholic fatty liver disease

Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity.

C-C Chemokine Receptor 2 (CCR2) Regulates the Hepatic Recruitment of Myeloid Cells That Promote Obesity-Induced Hepatic Steatosis

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 441

Cited by 31

Most referenced authors 1,122