Chemerin/CMKLR1 ameliorates nonalcoholic steatohepatitis by promoting autophagy and alleviating oxidative stress through the JAK2-STAT3 pathway

An, Xiuqin; Liu, Jinchun; Li, Yue; Dou, Zhangfeng; Li, Ning; Suo, Yuhong; Ma, Yanan; Sun, Meiqing; Tian, Zhongyuan; Xu, Lijun

doi:10.1016/j.peptides.2020.170422

Cited by 14 publications

(24 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its levels are directly associated with elements of MS, such as BMI, hypertension, high triglycerides, and C-reactive protein levels. Chemerin is elevated in obese and DM2 individuals and is inversely related to HDL-c and omentin levels [ 68 , 90 ].…”

Section: Organokinesmentioning

confidence: 99%

Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future

Santos

Maio

Lemes

et al. 2022

IJMS

View full text Add to dashboard Cite

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, and enlargement of the diameter of hepatocytes (ballooning hepatocytes), with or without fibrosis. It affects 20% of patients with non-alcoholic fatty liver disease (NAFLD). Due to liver dysfunction and the numerous metabolic changes that commonly accompany the condition (obesity, insulin resistance, type 2 diabetes, and metabolic syndrome), the secretion of organokines is modified, which may contribute to the pathogenesis or progression of the disease. In this sense, this study aimed to perform a review of the role of organokines in NASH. Thus, by combining descriptors such as NASH, organokines, oxidative stress, inflammation, insulin resistance, and dyslipidemia, a search was carried out in the EMBASE, MEDLINE-PubMed, and Cochrane databases of articles published in the last ten years. Insulin resistance, inflammation and mitochondrial dysfunction, fructose, and intestinal microbiota were factors identified as participating in the genesis and progression of NASH. Changes in the pattern of organokines secretion (adipokines, myokines, hepatokines, and osteokines) directly or indirectly contribute to aggravating the condition or compromise homeostasis. Thus, further studies involving skeletal muscle, adipose, bone, and liver tissue as endocrine organs are essential to better understand the modulation of organokines involved in the pathogenesis of NASH to advance in the treatment of this disease.

show abstract

Section: Organokinesmentioning

confidence: 99%

Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future

Santos

Maio

Lemes

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…A recent study showed that intraperitoneal injection of huChem-157 was protective in a high-fat diet model of NASH [ 30 ]. Hepatic and serum chemerin protein were approximately two-fold higher in these mice.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study described a protective role for huChem-157 injection in a high-fat diet model of NASH [ 30 ]. Hepatic steatosis, hepatocyte ballooning, and lobular and portal inflammation were all improved [ 30 ]. Notably, recombinant chemerin induced the hepatic mRNA expression of chemerin and CMKLR1 [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…Hepatic steatosis, hepatocyte ballooning, and lobular and portal inflammation were all improved [ 30 ]. Notably, recombinant chemerin induced the hepatic mRNA expression of chemerin and CMKLR1 [ 30 ]. In the experimental model described above endogenous chemerin protein was low in the NASH liver [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…Notably, recombinant chemerin induced the hepatic mRNA expression of chemerin and CMKLR1 [ 30 ]. In the experimental model described above endogenous chemerin protein was low in the NASH liver [ 30 ]. This finding has been contradicted by other studies which reported that hepatic chemerin expression was either not changed or induced in the murine NASH liver [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis

et al. 2022

View full text Add to dashboard Cite

Non-alcoholic steatohepatitis (NASH) is marked by macrophage infiltration and inflammation. Chemerin is a chemoattractant protein and is abundant in hepatocytes. The aim of this study was to gain insight into the role of hepatocyte-produced prochemerin in NASH. Therefore, mice were infected with adeno-associated virus 8 to direct hepatic overexpression of prochemerin in a methionine–choline deficient dietary model of NASH. At the end of the study, hepatic and serum chemerin were higher in the chemerin-expressing mice. These animals had less hepatic oxidative stress, F4/80 and CC-chemokine ligand 2 (CCL2) protein, and mRNA levels of inflammatory genes than the respective control animals. In order to identify the underlying mechanisms, prochemerin was expressed in hepatocytes and the hepatic stellate cells, LX-2. Here, chemerin had no effect on cell viability, production of inflammatory, or pro-fibrotic factors. Notably, cultivation of human peripheral blood mononuclear cells (PBMCs) in the supernatant of Huh7 cells overexpressing chemerin reduced CCL2, interleukin-6, and osteopontin levels in cell media. CCL2 was also low in RAW264.7 cells exposed to Hepa1–6 cell produced chemerin. In summary, the current study showed that prochemerin overexpression had little effect on hepatocytes and hepatic stellate cells. Of note, hepatocyte-produced chemerin deactivated PBMCs and protected against inflammation in experimental NASH.

show abstract

Hepatocyte expressed chemerin-156 does not protect from experimental non-alcoholic steatohepatitis

et al. 2022

View full text Add to dashboard Cite

Non-alcoholic steatohepatitis (NASH) is a rapidly growing liver disease. The chemoattractant chemerin is abundant in hepatocytes, and hepatocyte expressed prochemerin protected from NASH. Prochemerin is inactive and different active isoforms have been described. Here, the effect of hepatocyte expressed muChem-156, a highly active murine chemerin isoform, was studied in the methionine–choline deficient dietary model of NASH. Mice overexpressing muChem-156 had higher hepatic chemerin protein. Serum chemerin levels and the capability of serum to activate the chemerin receptors was unchanged showing that the liver did not release active chemerin. Notably, activation of the chemerin receptors by hepatic vein blood did not increase in parallel to total chemerin protein in patients with liver cirrhosis. In experimental NASH, muChem-156 had no effect on liver lipids. Accordingly, overexpression of active chemerin in hepatocytes or treatment of hepatocytes with recombinant chemerin did not affect cellular triglyceride and cholesterol levels. Importantly, overexpression of muChem-156 in the murine liver did not change the hepatic expression of inflammatory and profibrotic genes. The downstream targets of chemerin such as p38 kinase were neither activated in the liver of muChem-156 producing mice nor in HepG2, Huh7 and Hepa1-6 cells overexpressing this isoform. Recombinant chemerin had no effect on global gene expression of primary human hepatocytes and hepatic stellate cells within 24 h of incubation. Phosphorylation of p38 kinase was, however, increased upon short-time incubation of HepG2 cells with chemerin. These findings show that muChem-156 overexpression in hepatocytes does not protect from liver steatosis and inflammation.

show abstract

Chemerin/CMKLR1 ameliorates nonalcoholic steatohepatitis by promoting autophagy and alleviating oxidative stress through the JAK2-STAT3 pathway

Cited by 14 publications

References 47 publications

Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future

Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future

Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis

Hepatocyte expressed chemerin-156 does not protect from experimental non-alcoholic steatohepatitis

Contact Info

Product

Resources

About