Crosstalk between adipose tissue insulin resistance and liver macrophages in non-alcoholic fatty liver disease

Rosso, Chiara; Kazankov, Konstantin; Younes, Ramy; Esmaili, Saeed; Marietti, Milena; Sacco, Marco; Carli, Fabrizia; Gaggini, Melania; Salomone, Federico; Møller, Holger Jon; Abate, Maria Lorena; Vilstrup, Hendrik; Gastaldelli, Amalia; George, Jacob; Grønbæk, Henning; Bugianesi, Elisabetta

doi:10.1016/j.jhep.2019.06.031

Cited by 148 publications

(124 citation statements)

References 42 publications

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“…Macrophage scavenger receptors have been reported to play an important role in the metabolic 5 homeostasis in adipose tissue (14). In this study, we demonstrate an immunoregulatory role for MSR1 in the presence of lipids, highlighting the metabolic-inflammatory axis between the liver and adipose tissue (24,25). This process was shown to be independent of LPS (19), implementing that MSR1 is crucial in the early development of obesity-induced NAFLD.…”

Section: Fig 1 Macrophage Scavenger Receptor 1 (Msr1) Expression Insupporting

confidence: 54%

“…Consistently with enhanced adipose mass, HFD-fed Msr1 -/mice displayed larger adipocytes along with enhanced fatty acid accumulation within the cells and increased leptin serum levels compared 25 to WT mice, indicating an increased adiposity and fat storage in the absence of Msr1 ( Fig. 2c-d, Fig.…”

Section: Fig 1 Macrophage Scavenger Receptor 1 (Msr1) Expression Inmentioning

confidence: 54%

“…3b-d) (18). Furthermore, Msr1 deficiency did not reveal a reduced presence of macrophages neither in the eWAT nor in the liver but impaired pro-inflammatory macrophage activation represented by lower gene transcripts of Tnfa and Il6 in isolated adipose 25 tissue-(ATMs) and hepatic-associated macrophages ( Fig. 3e-g).…”

Section: Fig 1 Macrophage Scavenger Receptor 1 (Msr1) Expression Inmentioning

confidence: 81%

“…MSR1 is a key macrophage receptor for the clearance of circulating lipoproteins and has been implicated in atherogenesis (9,10). We therefore hypothesised that MSR1 might be involved in inflammatory responses in the context of lipid 25 overload during obesity-induced NAFLD.…”

Section: Main Textmentioning

confidence: 99%

“…Several single nucleotide polymorphisms (SNPs) have been associated with susceptibility to NAFLD (20)(21)(22). Using a cohort of 1,483 European Caucasian patients with histologicallyproven NAFLD and 17,781 European general-population controls, we identified 4 SNPs in or 25 around the MSR1 locus with p-values<5*10 -4 , with rs41505344 as the most significant (p=1,64E-04) ( Fig. 4f and Table S3).…”

Section: Fig 1 Macrophage Scavenger Receptor 1 (Msr1) Expression Inmentioning

confidence: 99%

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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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Section: Fig 1 Macrophage Scavenger Receptor 1 (Msr1) Expression Insupporting

confidence: 54%

Section: Fig 1 Macrophage Scavenger Receptor 1 (Msr1) Expression Inmentioning

confidence: 54%

Section: Fig 1 Macrophage Scavenger Receptor 1 (Msr1) Expression Inmentioning

confidence: 81%

Section: Main Textmentioning

confidence: 99%

Section: Fig 1 Macrophage Scavenger Receptor 1 (Msr1) Expression Inmentioning

confidence: 99%

See 3 more Smart Citations

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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Metabolic dysfunction and early‐onset colorectal cancer – how macrophages build the bridge

et al. 2020

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Background The incidence of colorectal cancer (CRC) among patients <50 years of age has increased dramatically over the last decades. At the same time, the growing proportion of obese children and adolescents and the increasing proportion of young and obese patients with CRC suggests an association between metabolic dysfunction and carcinogenesis. Tumor‐associated macrophages (TAMs) are able to orchestrate tumor promoting and suppressing mechanisms in CRC. The aim of this review was to discuss the different roles of TAMs in CRC and their phenotype‐specific metabolic pathways to identify potential new targets for CRC treatment. Methods A literature search was performed using PubMed, Cochrane and Embase to identify studies on TAMs and their metabolism in CRC. The following search terms were used in various combinations: (obesity OR adiposity OR obese) AND (macrophage OR polarization OR macrophage metabolism) AND ((colon cancer*) OR (colon carcinoma) OR (colonic tumor*) OR (colonic neoplasm[MeSH]) OR (rectal cancer*) OR (rectal carcinoma) OR (rectal tumor*) OR (rectal neoplasm[MeSH]) OR (colorectal cancer*) OR (colorectal carcinoma) OR (colorectal tumor*) OR (colorectal neoplasm[MeSH])). Studies including data on the phenotype and metabolism of TAMs in CRC were analyzed. Results Evidence for the prognostic utility of macrophage markers in CRC is currently evolving, with a particular role of stage‐dependent cellular metabolism profiles of TAMs. Itaconate is one of the metabolites produced by proinflammatory subtypes of TAMs and it is known to have tumor promoting effects. Metabolic pathways that are involved in macrophage activation and reprogramming play a role in a chronic inflammatory setting, consequently affecting the onset and development of CRC. Conclusions Tumor‐promoting metabolites, such as itaconate, are directly regulating these mechanisms, thereby triggering carcinogenesis. Metabolic reprogramming in TAMs can build a bridge between metabolic dysfunction and the onset and progression of CRC through inflammatory pathways, particularly in younger patients with early‐onset CRC.

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Clusterin is closely associated with adipose tissue insulin resistance

Wang

et al. 2023

Diabetes Metabolism Res

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AimsClusterin (encoded by CLU) is a novel adipokine. Serum clusterin levels were elevated in populations with obesity and diabetes. Adipose tissue insulin resistance (Adipo‐IR) is proposed as an early metabolic defect that precedes systemic insulin resistance. Herein, we aimed to investigate the relationship between serum clusterin levels and Adipo‐IR. CLU expression in human abdominal adipose tissues and clusterin secretion in human adipocytes was also explored.Materials and MethodsA total of 201 participants (aged 18–62 years, 139 of whom were obese) were recruited. Enzyme‐linked immunosorbent assay was used to measure serum clusterin levels. Adipo‐IR was calculated from the product of fasting free fatty acids and fasting insulin levels. Transcriptome sequencing of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was performed. Human adipocytes were used to detect the secretion of clusterin.ResultsSerum clusterin levels were independently associated with Adipo‐IR after adjusting for several confounding factors (standardised β = 0.165, p = 0.021). CLU expression in VAT and SAT was associated with obesity‐related metabolic risk factors. Higher CLU expression in VAT was accompanied by an increase in collagen accumulation. Clusterin secretion in differentiated human adipocytes was stimulated by insulin and inhibited by rosiglitazone.ConclusionsClusterin is strongly associated with Adipo‐IR. Serum clusterin may function as an effective indicator of adipose tissue insulin resistance.

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Crosstalk between adipose tissue insulin resistance and liver macrophages in non-alcoholic fatty liver disease

Cited by 148 publications

References 42 publications

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

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

Metabolic dysfunction and early‐onset colorectal cancer – how macrophages build the bridge

Clusterin is closely associated with adipose tissue insulin resistance

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