The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Kazankov, Konstantin; Baunwall, Simon Mark Dahl; Thomsen, Karen Louise; Møller, Holger Jon; Vilstrup, Hendrik; George, Jacob; Schuppan, Detlef; Grønbæk, Henning

doi:10.1038/s41575-018-0082-x

Cited by 696 publications

(619 citation statements)

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“…It is well known that insulin resistance, metabolic syndrome and its components play a crucial role in the pathophysiology of NAFLD‐related liver fibrosis, and skeletal muscle depletion, with its close correlation with insulin resistance and systemic metabolic status, can promote the NAFLD progression. However, unlike the direct regulation of hepatic lipogenesis by skeletal muscle, the progression of liver fibrosis in patients with skeletal muscle depletion appears to be more dependent on the excessive adiposity and adipose inflammation …”

Section: Discussionmentioning

confidence: 99%

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The PNPLA3 rs738409 C>G variant influences the association between low skeletal muscle mass and NAFLD: the Shanghai Changfeng Study

Xia

Chen

et al. 2019

Aliment Pharmacol Ther

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Summary Background Age‐related skeletal muscle loss and patatin‐like phospholipase domain‐containing 3 (PNPLA3) polymorphisms are both associated with increased liver steatosis and fibrosis in the absence of obesity. Aim To investigate the influence of PNPLA3 polymorphism on the relationship between skeletal muscle loss and non‐alcoholic fatty liver disease (NAFLD). Methods Liver fat content was measured using a quantitative ultrasound method, and liver fibrosis was assessed by NAFLD fibrosis, BARD and FIB‐4 scores in 3969 Chinese adults. The degree of sarcopenia was measured by weight‐adjusted appendicular skeletal muscle mass (ASM% = appendicular skeletal muscle mass(kg)/body weight(kg) 100%). Results The NAFLD proportion increased from 19.9% to 41.2% in men and 26.3% to 42.3% in women with decreasing ASM% quartiles (P < 0.001). Low ASM% was inversely associated with NAFLD in PNPLA3 CC (odds ratio [OR]: men, 0.735 [0.610‐0.885] and women, 0.812 [0.718‐0.918], both P = 0.001) and CG (OR: men, 0.673 [0.573‐0.790] and women, 0.798 [0.713‐0.893], both P < 0.001) but not GG genotype carriers. The association remained significant after adjustment for age, cigarette smoking, fat mass, interaction between fat mass and ASM%, obesity, diabetes and all components of metabolic syndrome. Subgroup analyses found that PNPLA3 GG gene variant did not increase the risk for NAFLD in individuals with low ASM% regardless of obesity status. Low ASM% also increased risk for liver fibrosis (all P < 0.05), which became insignificant after multiple adjustments. Conclusions Low ASM% is associated with NAFLD and liver fibrosis. Dissociation of sarcopenia and NAFLD was found in PNPLA3 GG genotype carriers. A stratification based on PNPLA3 genotypes might facilitate personalised treatment for NAFLD.

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Section: Discussionmentioning

confidence: 99%

“…Abbreviations: OR, odds ratio; ASM%, weight-adjusted appendicular skeletal muscle mass. direct regulation of hepatic lipogenesis by skeletal muscle, the progression of liver fibrosis in patients with skeletal muscle depletion appears to be more dependent on the excessive adiposity and adipose inflammation 45.…”

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confidence: 99%

The PNPLA3 rs738409 C>G variant influences the association between low skeletal muscle mass and NAFLD: the Shanghai Changfeng Study

Xia

Chen

et al. 2019

Aliment Pharmacol Ther

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“…The patient had hepatomegaly, but nonalcoholic fatty liver disease could not be proven radiographically, and biopsy was deferred. Over 99% of IV bacteriophage therapy is rapidly cleared by the liver and spleen [13][14][15]. This research team's theory is that underlying steatosis caused liver macrophages to induce a dysregulated local cytokine response when challenged with large numbers of bacteriophages that needed to be hepatically cleared.…”

Section: Discussionmentioning

confidence: 99%

Salvage Bacteriophage Therapy for a Chronic MRSA Prosthetic Joint Infection

Doub

Johnson

et al. 2020

Antibiotics

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“…DAVID annotation tool was used for pathway enrichment. (3,4) Data were visualized with GOPlot (7,8). For the present study, we restricted our analysis to a subset of UK Biobank participants with European ancestry by adding individuals who self-reported as being 'Irish' or 'Any other white background' (after removal of outliers based on first 2 genetic principal components) to the subset 10 of white British ancestry (7,9).…”

Section: Mass Spectrometry Data Analysismentioning

confidence: 99%

Macrophage Scavenger Receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease

Govaere

Martínez–López

Petersen

et al. 2020

Preprint

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Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), however the exact mechanisms remain incompletely understood. Here we demonstrate that macrophage scavenger receptor 1 (MSR1) is associated with the occurrence of hepatic lipid-laden foamy macrophages and correlates with the degree of steatosis and steatohepatitis in a large cohort of NAFLD patients. Mice lacking Msr1 are protected against high fat diet-induced metabolic disorder, showing less hepatic inflammation and fibrosis, reduced circulating fatty acids, increased lipid storage in the adipocytes and improved glucose tolerance. Moreover, MSR1 triggers diet-induced JNK-mediated inflammatory activation of macrophages independent of lipopolysaccharide. Taken together, our data suggest a critical role for MSR1 in lipid homeostasis and a potential therapeutic target for the treatment of NAFLD.One Sentence SummaryThe immunometabolic role of MSR1 in human NAFLD.

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The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Cited by 696 publications

References 195 publications

The PNPLA3 rs738409 C>G variant influences the association between low skeletal muscle mass and NAFLD: the Shanghai Changfeng Study

The PNPLA3 rs738409 C>G variant influences the association between low skeletal muscle mass and NAFLD: the Shanghai Changfeng Study

Salvage Bacteriophage Therapy for a Chronic MRSA Prosthetic Joint Infection

Macrophage Scavenger Receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease

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