Silencing CCR2 in Macrophages Alleviates Adipose Tissue Inflammation and the Associated Metabolic Syndrome in Dietary Obese Mice

Kim, Jong-Kil; Chung, Ki-Seok; Choi, Chang Gyu; Beloor, Jagadish; Ullah, Irfan; Kim, Nahyeon; Lee, Kuen Yong; Lee, Sangkyung; Kumar, Priti

doi:10.1038/mtna.2015.51

Cited by 50 publications

(43 citation statements)

References 89 publications

(138 reference statements)

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“…In Ccr2 2/2 mice fed a highfat diet, a reduction in food intake, macrophage recruitment, inflammatory markers in adipose tissue, and an improvement in glucose homeostasis and insulin sensitivity have been reported (Weisberg et al, 2006). A similar phenotype has also been described with siRNA knockdown of CCR2 (Kim et al, 2016). In global Ccr2 2/2 and hematopoietic (bone marrow) Ccr2 2/2 mice fed a high-fat diet for 12 weeks, flow cytometry revealed differences in the F4/80 + myeloid cell population compared with their wild-type counterparts.…”

Section: G Protein-coupled Receptors and Obesity-induced Type 2 mentioning

confidence: 71%

G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

Riddy¹,

Delerive²,

Summers³

et al. 2018

Pharmacological Reviews

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G protein-coupled receptors (GPCRs) continue to be important discovery targets for the treatment of type 2 diabetes mellitus (T2DM). Many GPCRs are directly involved in the development of insulin resistance and -cell dysfunction, and in the etiology of inflammation that can lead to obesity-induced T2DM. This review summarizes the current literature describing a number of well-validated GPCR targets, but also outlines several new and promising targets for drug discovery. We highlight the importance of understanding the role of these receptors in the disease pathology, and their basic pharmacology, which will pave the way to the development of novel pharmacological probes that will enable these targets to fulfill their promise for the treatment of these metabolic disorders.

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Section: G Protein-coupled Receptors and Obesity-induced Type 2 mentioning

confidence: 71%

G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

Riddy¹,

Delerive²,

Summers³

et al. 2018

Pharmacological Reviews

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show abstract

“…Indeed, dampening ATM accumulation and consequent inflammation, via monocyte chemoattractant CCL2/CCR2 pharmacological inhibition, Tamura et al [50] showed an improvement of obesity and related metabolic disorders, such as insulin resistance and hepatic steatosis in db/db mice. Moreover, recently it has been reported that macrophage-targeted delivery of small interference RNA against CCR2 inhibited ATM recruitment and accumulation in adipose tissue, thus reducing the downstream effects of obesity-induced inflammation [72]. …”

Section: Adipose Tissue Inflammationmentioning

confidence: 99%

The Role of Tissue Macrophage-Mediated Inflammation on NAFLD Pathogenesis and Its Clinical Implications

Alisi

Carpino

Oliveira

et al. 2017

Mediators of Inflammation

152

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The obese phenotype is characterized by a state of chronic low-grade systemic inflammation that contributes to the development of comorbidities, including nonalcoholic fatty liver disease (NAFLD). In fact, NAFLD is often associated with adipocyte enlargement and consequent macrophage recruitment and inflammation. Macrophage polarization is often associated with the proinflammatory state in adipose tissue. In particular, an increase of M1 macrophages number or of M1/M2 ratio triggers the production and secretion of various proinflammatory signals (i.e., adipocytokines). Next, these inflammatory factors may reach the liver leading to local M1/M2 macrophage polarization and consequent onset of the histological damage characteristic of NAFLD. Thus, the role of macrophage polarization and inflammatory signals appears to be central for pathogenesis and progression of NAFLD, even if the heterogeneity of macrophages and molecular mechanisms that govern their phenotype switch remain incompletely understood. In this review, we discuss the role of adipose and liver tissue macrophage-mediated inflammation in experimental and human NAFLD. This focus is relevant because it may help researchers that approach clinical and experimental studies on this disease advancing the knowledge of mechanisms that could be targeted in order to revert NAFLD-related fibrosis.

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“…Similar effects were observed in vivo in diet-induced obese mice, which showed decreased numbers of infiltrated monocytes into the injured liver. In addition,~70% reduction in TNF-α levels and complete reversal of steatosis was evidenced [29]. These results indicate that strategies comprising cell-targeted gene knockdown through miRNA/siRNA are promising therapeutic approaches for the treatment of various liver diseases.…”

Section: Mirna/sirna-based Approachesmentioning

confidence: 78%

Therapeutic Targeting of Hepatic Macrophages

Nijland

Bansal²

2020

Curr. Tissue Microenviron. Rep.

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Purpose of Review This review outlines the current knowledge about hepatic macrophages and provides an overview of therapeutic approaches to target hepatic macrophages for the treatment of liver diseases. Recent Findings In recent years, it has been increasingly recognized that hepatic macrophages (resident macrophages, Kupffer cells, or circulating bone marrow monocyte-derived macrophages) are implicated in liver homeostasis as well as in disease progression and resolution. More recently, different populations of hepatic macrophages with distinct phenotypes and functions have been identified that have shown to play distinct roles in the pathogenesis of various acute and chronic liver diseases. The understanding of the role of hepatic macrophages in initiation, progression, and resolution of liver diseases has given rise to the development of therapeutics that can target different phenotypes of hepatic macrophages. Innovative strategies comprises of microRNA (miRNA), small interfering RNA (siRNA), therapeutic proteins, and small-molecule inhibitors. Summary Evidence from recent in vitro and in vivo studies support the fact that hepatic macrophages can be efficiently targeted using miRNA/siRNA-based approaches, protein-based approaches, and small-molecule inhibitors for the treatment of liver diseases. However, more in-depth understanding underlying the roles of distinct macrophage phenotypes in different liver diseases is required for the translation of novel targeted therapeutics to the clinic. Keywords Hepatic macrophages. Targeted therapeutics. Liver diseases. Monocytes. Kupffer cells This article is part of the Topical Collection on Chronic Liver Disease

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Silencing CCR2 in Macrophages Alleviates Adipose Tissue Inflammation and the Associated Metabolic Syndrome in Dietary Obese Mice

Cited by 50 publications

References 89 publications

G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

The Role of Tissue Macrophage-Mediated Inflammation on NAFLD Pathogenesis and Its Clinical Implications

Therapeutic Targeting of Hepatic Macrophages

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