MSP: An emerging player in metabolic syndrome

Li, Jieyi; Chanda, Dipanjan; Shiri-Sverdlov, Ronit; Neumann, Dietbert

doi:10.1016/j.cytogfr.2014.10.007

Cited by 17 publications

(18 citation statements)

References 86 publications

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“…Subsequent evidences pointed out a correlation between MSP and liver injury; for example, MSP was transcriptionally up-regulated in the liver during hepatic inflammation and regeneration in rodent models [ 17 ]. Currently, the investigations of MSP in the context of hepatic inflammation are relatively limited, and are restricted to inflammation that is induced by exogenous substances [ 18 ]. Whereas MSP has emerged as a beneficial moderator in hepatic lipid and glucose metabolism [ 7 , 8 , 18 ], the role of MSP in the context of the metabolic syndrome, especially in metabolic inflammation, has not been explored.…”

Section: Discussionmentioning

confidence: 99%

Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model

Chanda

Gorp

et al. 2016

PLoS ONE

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Non-alcoholic steatohepatitis (NASH) is a common liver disease characterized by hepatic lipid accumulation (steatosis) and inflammation. Currently, therapeutic options are poor and the long-term burden to society is constantly increasing. Previously, macrophage stimulating protein (MSP)—a serum protein mainly secreted by liver—was shown to inhibit oxidized low-density lipoprotein (OxLDL)/lipopolysaccharides (LPS)-induced inflammation in mouse macrophages. Additionally, MSP could reduce palmitic acid (PA)-induced lipid accumulation and lipogenesis in the HepG2 cell line. Altogether, these data suggest MSP as a suppressor for metabolic inflammation. However, so far the potential of MSP to be used as a treatment for NASH was not investigated. We hypothesized that MSP reduces lipid accumulation and hepatic inflammation. To investigate the effects of MSP in the early stage of NASH, low-density lipoprotein receptor (Ldlr-/-) mice were fed either a regular chow or a high fat, high cholesterol (HFC) diet for 7 days. Recombinant MSP or saline (control) was administrated to the mice by utilizing subcutaneously-implanted osmotic mini-pumps for the last 4 days. As expected, mice fed an HFC diet showed increased plasma and hepatic lipid accumulation, as well as enhanced hepatic inflammation, compared with chow-fed controls. Upon MSP administration, the rise in cholesterol and triglyceride levels after an HFC diet remained unaltered. Surprisingly, while hepatic macrophage and neutrophil infiltration was similar between the groups, MSP-treated mice showed increased gene expression of pro-inflammatory and pro-apoptotic mediators in the liver, compared with saline-treated controls. Contrary to our expectations, MSP did not ameliorate NASH. Observed changes in inflammatory gene expression suggest that further research is needed to clarify the long-term effects of MSP.

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Section: Discussionmentioning

confidence: 99%

Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model

Chanda

Gorp

et al. 2016

PLoS ONE

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“…MSP suppresses inflammation by inhibiting NF-kB signaling and activating the PI3-kinase and AMPK-SHP pathways, which in turn reduce inducible nitric oxide synthase (iNOS) production in macrophages and cyclooxygenase-2 and inhibit the expression of pro-inflammatory cytokines, such as IL-12. HGF exhibits antiinflammatory effects and promotes glucose uptake, insulin sensitivity and suppression of hepatic lipid accumulation and steatosis (Li et al, 2015a). Additional hepatokines include fetuin-A, an adaptor for binding of saturated fatty acids to TLR4, which stimulates adipose tissue inflammation and results in insulin resistance (Pal et al, 2012), TGF-b (Yang et al, 2014a), and MCP-1 (Baeck et al, 2012).…”

Section: Non-hematopoietic Mediators Of the Metabolic Syndromementioning

confidence: 99%

The Role of the Immune System in Metabolic Health and Disease

et al. 2017

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In addition to the immune system's traditional roles of conferring anti-infectious and anti-neoplastic protection, it has been recently implicated in the regulation of systemic metabolic homeostasis. This cross-talk between the immune and the metabolic systems is pivotal in promoting "metabolic health" throughout the life of an organism and plays fundamental roles in its adaptation to ever-changing environmental makeups and nutritional availability. Perturbations in this intricate immune-metabolic cross-talk contribute to the tendency to develop altered metabolic states that may culminate in metabolic disorders such as malnutrition, obesity, type 2 diabetes mellitus (T2DM), and other features of the metabolic syndrome. Regulators of immune-metabolic interactions include host genetics, nutritional status, and the intestinal microbiome. In this Perspective, we highlight current understanding of immune-metabolism interactions, illustrate differences among individuals and between populations in this respect, and point toward future avenues of research possibly enabling immune harnessing as means of personalized treatment for common metabolic disorders.

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“…The results shown in this study are consistent with the phenotype of mice with a targeted deletion of the ligand for Ron, MSP, which develop hepatic steatosis. In addition, a number of recent reports point to a beneficial role for MSP in regulating hepatic lipid and glucose homeostasis, and a potential therapeutic use of MSP in treating metabolic syndrome has been suggested (43). There is extensive cross-talk between Ron and the closely related Met receptor and its ligand, hepatocyte growth factor, which plays a critical role in the liver (44).…”

Section: The Journal Of Immunologymentioning

confidence: 99%

The Ron Receptor Tyrosine Kinase Regulates Macrophage Heterogeneity and Plays a Protective Role in Diet-Induced Obesity, Atherosclerosis, and Hepatosteatosis

Allen

Dey

et al. 2016

The Journal of Immunology

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Obesity is a chronic inflammatory disease mediated in large part by the activation of inflammatory macrophages. This chronic inflammation underlies a whole host of diseases including atherosclerosis, hepatic steatosis, insulin resistance, type 2 diabetes, and cancer, among others. Macrophages are generally classified as either inflammatory or alternatively activated. Some tissue-resident macrophages are derived from yolk sac erythromyeloid progenitors and fetal liver progenitors that seed tissues during embryogenesis and have the ability to repopulate through local proliferation. These macrophages tend to be anti-inflammatory in nature and are generally involved in tissue remodeling, repair, and homeostasis. Alternatively, during chronic inflammation induced by obesity, bone marrow monocyte-derived macrophages are recruited to inflamed tissues, where they produce proinflammatory cytokines and exacerbate inflammation. The extent to which these two populations of macrophages are plastic in their phenotype remains controversial. We have demonstrated previously that the Ron receptor tyrosine kinase is expressed on tissue-resident macrophages, where it limits inflammatory macrophage activation and promotes a repair phenotype. In this study, we demonstrate that Ron is expressed in a subpopulation of macrophages during chronic inflammation induced by obesity that exhibit a repair phenotype as determined by the expression of arginase 1. In addition, we demonstrate that the Ron receptor plays a protective role in the progression of diet-induced obesity, hepatosteatosis, and atherosclerosis. These results suggest that altering macrophage heterogeneity in vivo could have the potential to alleviate obesity-associated diseases.

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MSP: An emerging player in metabolic syndrome

Cited by 17 publications

References 86 publications

Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model

Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model

The Role of the Immune System in Metabolic Health and Disease

The Ron Receptor Tyrosine Kinase Regulates Macrophage Heterogeneity and Plays a Protective Role in Diet-Induced Obesity, Atherosclerosis, and Hepatosteatosis

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