Metformin improves obesity-associated inflammation by altering macrophages polarization

Jing, Yuanyuan; Wu, Fan; Li, Dai; Yang, Lei; Li, Qi; Li, Rong

doi:10.1016/j.mce.2017.09.025

Cited by 176 publications

(110 citation statements)

References 29 publications

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“…Recently published studies revealed a potential role of metformin in improving the effective treatment of TB and indicated that metformin is a promising candidate adjunctive therapy for individuals with TB . A previously published study reports that metformin improves the chronic low‐grade inflammatory state and also alters the macrophage polarization both in vivo and in vitro . Our current findings provide additional evidence of a host‐directed therapeutic effect for metformin based on decreased systemic levels of sCD14, sCD163 and CRP.…”

Section: Discussionsupporting

confidence: 69%

Elevated circulating levels of monocyte activation markers among tuberculosis patients with diabetes co‐morbidity

et al. 2018

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Alteration in the frequency of monocyte subsets is a hallmark of tuberculosis-diabetes co-morbidity (TB-DM). To study this association, we examined the plasma levels of sCD14, sCD163, C-reactive protein (CRP) and soluble tissue factor (sTF) in individuals with TB-DM, TB or diabetes mellitus (DM), and in healthy controls (HC). Circulating levels of sCD14, sCD163 and sTF were significantly increased in TB-DM and DM compared with TB and HC; however, CRP was significantly increased in TB-DM and TB compared with DM and HC. During longitudinal follow up, sCD14, CRP and sTF levels remained significantly increased in TB-DM compared with TB from baseline (pre-treatment), during treatment (2nd month) and at the completion (6th month) of anti-TB treatment (ATT), whereas sCD163 was significantly higher in TB-DM compared with TB only at baseline. Moreover, the levels of sCD14 and sCD163 were significantly higher in TB-DM individuals with bilateral and cavitary disease and exhibited a significant positive relationship with bacterial burden. Levels of sCD14, sCD163 and CRP exhibited a positive relationship with HbA1c levels. Within the TB-DM group, those with known diabetes before incident TB (KDM) exhibited significantly higher levels of sCD14 and sCD163 compared with individuals with newly diagnosed DM with TB (NDM). Finally, KDM individuals on metformin treatment exhibited significantly lower levels of sCD14, sCD163 and CRP compared with those on non-metformin-containing regimens. Our data demonstrate that systemic monocyte activation marker levels reflect baseline disease severity and extent in TB-DM, differentiate KDM from NDM and are modulated by ATT and metformin therapy.

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Section: Discussionsupporting

confidence: 69%

Elevated circulating levels of monocyte activation markers among tuberculosis patients with diabetes co‐morbidity

et al. 2018

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“…No change was observed in HCC larvae treated with Metformin in the presence of a normal diet ( Fig.6A and B), suggesting the effect may be specific to HCD-induced progression. Consistent with prior studies suggesting that metformin alters macrophage polarization in vitro (44,45), we found that metformin treatment reduced the total number and density of TNFα-positive cells in the liver area in HCC+HCD larvae in vivo ( Fig.6C and D), suggesting that TNFα polarization of macrophages could play a role in NAFLD/NASH-associated HCC progression.…”

Section: Metformin Alters Macrophage Polarization and Hcc Progressionsupporting

confidence: 91%

High cholesterol diet modulates macrophage polarization and liver inflammation during early hepatocellular carcinoma progression in zebrafish

Oliveira

Houseright

Graves

et al. 2018

Preprint

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Abbreviations used in this paper: NAFLD, Nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; HCC, hepatocellular carcinoma; HCD, high-cholesterol diet; TME, tumor microenvironment; TNF, tumor necrosis factor; dpf, days post-fertilization; ND, normal diet; MTZ, metronidazole; NTR, nitroreductase. AbstractDiabetes and obesity have been associated with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and increased incidence of hepatocellular carcinoma (HCC). Here we use optically transparent zebrafish to visualize liver inflammation and disease progression in a NAFLD/NASH-HCC model. We combined a high-cholesterol diet (HCD) with a transgenic zebrafish HCC model induced by hepatocyte-specific activated βcatenin and found that diet induced an increase in liver size and enhanced angiogenesis and neutrophil infiltration in the liver. Although macrophage number was not affected by diet, HCD induced changes in macrophage morphology and polarization with an increase in liver associated TNFα-positive macrophages. Treatment with metformin altered macrophage polarization and reduced liver size in NAFLD/NASH-associated HCC larvae. Moreover, ablation of macrophages limited progression in NAFLD/NASH-associated HCC larvae but not in HCC alone. These findings suggest that HCD alters macrophage polarization and exacerbates the liver inflammatory microenvironment and cancer progression in a zebrafish model of NAFLD/NASH-associated HCC.

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“…Metformin exerts anti‐inflammatory effects on adipose tissue and decreases the release of proinflammatory adipokines from the epicardium . Accordingly, use of the biguanide has been accompanied by a decreased risk for AF and its associated thromboembolic events and by amelioration of diastolic filling abnormalities in experimental and clinical HFpEF .…”

Section: Therapeutic Challenges In Patients With a Metabolic Disordermentioning

confidence: 99%

“…Metformin exerts anti-inflammatory effects on adipose tissue and decreases the release of proinflammatory adipokines from the epicardium. [158][159][160] Accordingly, use of the biguanide has been accompanied by a decreased risk for AF and its associated thromboembolic events and by amelioration of diastolic filling abnormalities in experimental and clinical HFpEF. [161][162][163][164] Newer glucose-lowering drugs have been evaluated in large-scale trials, but, in most cases, these investigations did not systematically identify AF events and hence the number of captured AF events was too small to allow for meaningful analysis.…”

Section: Metformin and Sodium-glucose Cotransporter 2 Inhibitorsmentioning

confidence: 99%

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

Packer

2019

European J of Heart Fail

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Obesity and diabetes can lead to heart failure with preserved ejection fraction (HFpEF), potentially because they both cause expansion and inflammation of epicardial adipose tissue and thus lead to microvascular dysfunction and fibrosis of the underlying left ventricle. The same process also causes an atrial myopathy, which is clinically evident as atrial fibrillation (AF); thus, AF may be the first manifestation of HFpEF. Many patients with apparently isolated AF have latent HFpEF or subsequently develop HFpEF. Most patients with obesity or diabetes who have AF and exercise intolerance have increased left atrial pressures at rest or during exercise, even in the absence of diagnosed HFpEF. Among patients with AF, those who also have latent HFpEF have increased risk for systemic thromboembolism and death. The identification of HFpEF in patients with obesity or diabetes alters the risk‐to‐benefit relationship of commonly prescribed treatments. Bariatric surgery and statins can ameliorate AF and reduce the risk for HFpEF. Conversely, antihyperglycaemic drugs that promote adipogenesis or cause sodium retention (insulin and thiazolidinediones) may increase the risk for heart failure in patients with an underlying ventricular myopathy. Patients with obesity and diabetes who undergo catheter ablation for AF are at increased risk for AF recurrence and for post‐ablation increases in pulmonary venous pressures and worsening heart failure, especially if HFpEF coexists. Therefore, AF may be the earliest indicator of HFpEF in patients with obesity or type 2 diabetes, and recognition of HFpEF alters the management of these patients.

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Metformin improves obesity-associated inflammation by altering macrophages polarization

Cited by 176 publications

References 29 publications

Elevated circulating levels of monocyte activation markers among tuberculosis patients with diabetes co‐morbidity

Elevated circulating levels of monocyte activation markers among tuberculosis patients with diabetes co‐morbidity

High cholesterol diet modulates macrophage polarization and liver inflammation during early hepatocellular carcinoma progression in zebrafish

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

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