Deficiency of Oncostatin M Receptor β (OSMRβ) Exacerbates High-fat Diet-induced Obesity and Related Metabolic Disorders in Mice

Komori, Tadasuke; Tanaka, Minoru; Senba, Emiko; Miyajima, Atsushi; Morikawa, Yoshihiro

doi:10.1074/jbc.m113.542399

Cited by 39 publications

(57 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, obesity and related metabolic diseases, including hepatic steatosis, were exacerbated in mice deficient in OSMRβ under high-fat diet (HFD) conditions [15]. These findings suggest that OSM has beneficial effects on the development of obesity, adipose tissue inflammation, insulin resistance and hepatic steatosis.…”

Section: Introductionmentioning

confidence: 71%

“…Immunohistochemistry Immunofluorescence staining in the hypothalamus and liver was performed as previously described [15]. The mice were deeply anaesthetised with isoflurane and transcardially perfused with ice-cold 0.85% (wt/vol.)…”

Section: Methodsmentioning

confidence: 99%

“…Western blot analysis Western blot analysis was performed as previously described [14,15]. Tissue lysates were prepared using radioimmune precipitation assay (RIPA) buffer (Upstate Biotechnology, Lake Placid, NY, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Isolation of ATMs and flow cytometry Stromal vascular fraction (SVF) isolation and flow cytometry were performed as described previously [14,15]. The primary antibodies used in the flow cytometry are shown in ESM Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…In the pair-feeding experiments, paired-fed mice were given vehicle and the same amount of food as that consumed by OSM-treated mice. To investigate the direct effects of OSM on the liver, DIO mice were deeply anaesthetised with isoflurane and administered intraportally with vehicle or OSM (12.5 ng/g BW) as described previously [15].…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Oncostatin M is a potential agent for the treatment of obesity and related metabolic disorders: a study in mice

et al. 2015

Self Cite

View full text Add to dashboard Cite

Aims/hypothesis Obesity and insulin resistance are closely associated with adipose tissue dysfunction caused by the abnormal recruitment of inflammatory cells, including macrophages. Oncostatin M (OSM), a member of the IL-6 family of cytokines, plays important roles in a variety of biological functions including the regulation of inflammatory responses. In previous reports, we have demonstrated that mice deficient in the OSM receptor β subunit show obesity, adipose tissue inflammation, insulin resistance and hepatic steatosis, all of which are exacerbated by feeding the mice a high-fat diet. These results prompted us to test the therapeutic effects of OSM on obesity-induced metabolic disorders using mouse models of obesity. Methods In diet-induced obese and ob/ob mice, metabolic variables were assessed physiologically, histologically and biochemically after the intraperitoneal injection of recombinant mouse OSM twice a day for 1 week.Results Treatment with OSM improved obesity, adipose tissue inflammation, insulin resistance and hepatic steatosis in both mouse models. Although OSM reduced food intake, such therapeutic effects of OSM were observed even under pair-feeding conditions. Functionally, OSM directly changed the phenotype of adipose tissue macrophages from M1 type (inflammatory) to M2 type (anti-inflammatory). In the liver, OSM suppressed the expression of genes related to fatty acid synthesis and increased the expression of genes related to fatty acid oxidation. Furthermore, OSM decreased lipid absorption and increased the expression of active glucagon-like peptide-1 in the intestine. Conclusions/interpretation We showed that OSM is a novel candidate to act as a powerful therapeutic agent for the treatment of obesity-induced metabolic disorders.

show abstract

Section: Introductionmentioning

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Oncostatin M is a potential agent for the treatment of obesity and related metabolic disorders: a study in mice

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

LINC00520 targeting miR‐27b‐3p regulates OSMR expression level to promote acute kidney injury development through the PI3K/AKT signaling pathway

Tian

Liang

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Background Acute kidney injury (AKI) shows several kinds of disorders, which acutely harm the kidney. However, the current medical methods have limited therapeutic effects. The present study aimed to find out the molecular mechanism of AKI pathogenesis, which may provide new insights for future therapy. Methods Bioinformatic analysis was conducted using the R language (AT&T BellLaboratories, University of Auckland, New Zealand) to acquire the differentially expressed long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in AKI. The expression levels of RNAs and related proteins in tissues and cells were detected by quantitative real‐time PCR (qRT‐PCR) and western blot. Dual‐luciferase reporter gene assays were performed to verify the target relationship between microRNA (miRNA) and lncRNA as well as miRNA and mRNA. Flow cytometry and tunnel assay were used to detect the cell apoptotic rate in AKI. Results LINC00520, miR‐27b‐3p, and OSMR form an axis to regulate AKI. Knockdown of LINC00520 reduced acute renal injury both in vitro and in vivo. LINC00520 activated the PI3K/AKT pathway to aggravate renal ischemia/reperfusion injury, while upregulation of miR‐27b‐3p or downregulation of OSMR could accelerate the recovery of AKI. Conclusion Overexpression of LINC00520 contributes to the aggravation of AKI by targeting miR‐27b‐3p/ OSMR.

show abstract

The regulation and functions of ACSL3 and ACSL4 in the liver and hepatocellular carcinoma

Liu

Waugh

2022

Liver Cancer International

View full text Add to dashboard Cite

Altered cellular energetics is one of the hallmarks of cancer 1,2 and intratumoural lipid metabolism tends to be markedly changed in hepatocellular carcinoma (HCC) 1,[3][4][5] where it manifests as altered intracellular levels triacylglycerol (TAG), phospholipids, cholesterol and ceramide. 3,[6][7][8][9][10][11][12][13][14][15][16][17][18][19] HCC is one of the world's most common cancers 20,21 and can develop from chronic liver diseases that feature dysregulated lipid metabolism, inflammation and hepatocellular death. This pathological sequence is illustrated well in the case of non-alcoholic fatty liver disease (NAFLD) which can lead to nonalcoholic steatohepatitis (NASH) 21,22 and ultimately NASH-HCC. 23 Rewired lipid metabolism in HCC can also be characteristic of different oncogene driver mutations. For example, hepatomas with a CNNTB1 mutation encoding β-catenin are generally 'addicted' to mitochondrial fatty acid β-oxidation (FAO) 24 and have low levels of

show abstract

Deficiency of Oncostatin M Receptor β (OSMRβ) Exacerbates High-fat Diet-induced Obesity and Related Metabolic Disorders in Mice

Cited by 39 publications

References 53 publications

Oncostatin M is a potential agent for the treatment of obesity and related metabolic disorders: a study in mice

Oncostatin M is a potential agent for the treatment of obesity and related metabolic disorders: a study in mice

LINC00520 targeting miR‐27b‐3p regulates OSMR expression level to promote acute kidney injury development through the PI3K/AKT signaling pathway

The regulation and functions of ACSL3 and ACSL4 in the liver and hepatocellular carcinoma

Contact Info

Product

Resources

About