Osteoprotegerin Promotes Liver Steatosis by Targeting the ERK–PPAR-γ–CD36 Pathway

Zhang, Cheng; Luo, Xu; Chen, Jianrong; Zhou, Baoyong; Yang, Gangyi; Li, Rui; Liu, Dongfang; Gu, Harvest F.; Zhu, Zhiming; Wang, Cong-Yi

doi:10.2337/db18-1055

Cited by 70 publications

(60 citation statements)

References 53 publications

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“…Insulin resistance (IR) is the pathophysiological basis of metabolic diseases, such as type 2 diabetes mellitus (T2DM), metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) [1][2][3][4]. Increased IR in T2DM patients, obesity and MetS individuals is a high-risk factor for cardiovascular disease (CVD) [5][6].…”

Section: Introductionmentioning

confidence: 99%

Association of metabolic syndrome components with circulating levels of cytokine clusters in young women

Tan

Hu²,

Yang

et al. 2021

Endocrine Connections

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Background: The purpose of this study was to investigate the relationship between circulating zinc α 2-glycoprotein (ZAG), Irisin, betatrophin and adiponectin concentrations and metabolic syndrome (MetS) components and to analyze the effects of blood glucose and insulin on these cytokine concentrations in vivo. Methods: A total of 196 young women, including 78 healthy women and 118 women with MetS components, were recruited for this cross-sectional study. An oral glucose tolerance test and euglycemic-hyperinsulinemic clamp (EHC) were performed in healthy subjects and women with MetS components. An enzyme-linked immunosorbent assay kit was used to measure serum ZAG, irisin, betatrophin, and adiponectin levels, and their relationship with the MetS components was analyzed. Results: In women with MetS components, circulating irisin and betatrophin levels were significantly higher than those in the healthy women, but circulating ZAG and adiponectin levels were significantly lower . FBG, WC, and Triglyceride were significantly correlated with the circulating levels of these four cytokines (p < 0.001 or < 0.05). All four cytokines were associated with MetS and its components. In response to increasing insulin levels, circulating ZAG concentrations were markedly increased in both healthy subjects and women with MetS components during the EHC. However, serum irisin, betatrophin, and adiponectin levels in both healthy subjects and women with MetS components were significantly reduced compared with baseline. Conclusion: Serum ZAG, Irisin, betatrophin and adiponectin were associated with MetS and might be biomarkers for screening MetS components.

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Section: Introductionmentioning

confidence: 99%

Association of metabolic syndrome components with circulating levels of cytokine clusters in young women

Tan

Hu²,

Yang

et al. 2021

Endocrine Connections

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“…Peroxisome proliferator-activated receptor gamma (PPARγ), a number of the nuclear hormone receptor family, exerts a crucial role in mediating inflammatory diseases (e.g., colitis [14], liver steatosis [15], and rheumatoid arthritis [16]) and inflammatory and neuropathic pain development [17].…”

Section: Introductionmentioning

confidence: 99%

Pioglitazone Attenuates Experimental Colitis-Associated Hyperalgesia through Improving the Intestinal Barrier Dysfunction

et al. 2020

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Impaired intestinal mucosal integrity during colitis involves the peroxisome proliferator-activated receptor-γ (PPARγ), an important anti-inflammatory factor in intestinal mucosa homoeostasis, which is a potential target in colitis. Recurrent chronic pain is a vital pathogenetic feature of colitis. Nevertheless, potential functions of PPARγ in the colitis-associated hyperalgesia remain unclear. This study aimed to investigate biological roles of pioglitazone in relieving colitis-associated pain hypersensitivity by a PPARγ tight junction protein-dependent mechanism during the course of dextran sodium sulfate (DSS)-induced intestinal inflammation. The DSS-induced colitis model was generated in C57BL/6 mice. Changes in colitis induced the injury of intestinal mucosal barrier and hyperalgesia after a 6-day treatment of pioglitazone (25 mg/kg, IP injection) were assessed through immunofluorescent, hematoxylin and eosin (H&E) staining, western blot analysis, and determination of paw withdrawal mechanical threshold. A significant reduction of paw withdrawal mechanical threshold occurred after DSS treatment. Follow-up data showed that systematic administration of PPARγ agonist pioglitazone ameliorated the DSS-induced colitis and the development of colitis-associated hyperalgesia by repairing the intestinal mucosal barrier. The tight junction proteins ZO-1 and Claudin-5 were upregulated by PPARγ signaling, which in turn promoted the improvement of intestinal barrier function. Moreover, pioglitazone inhibited phosphorylation of ERK and NF-κB in the colon and decreased the levels of inflammatory cytokines in both colon spine tissues. Furthermore, systemically pioglitazone treatment inhibited the activation of microglia and astrocytes, as well as DSSinduced phosphorylation of NR2B subunit in spinal cord, which was correspondingly consistent with the pain behavior. Pioglitazone ameliorates DSS-induced colitis and attenuates colitis-associated mechanical hyperalgesia, with improving integrity of the Yulin Huang and Chenchen Wang contributed equally to this work.

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“…More importantly, CD36 is also involved in regulating chronic metabolic inflammation by activating the JNK pathway (Kennedy et al, 2011). A recent study suggested that osteoprotegerin (OPG) can regulate CD36 transcription through the ERK-PPARγ pathway, thus promoting hepatic steatosis (Zhang et al, 2019a).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-20a-5p Ameliorates Non-alcoholic Fatty Liver Disease via Inhibiting the Expression of CD36

Wang

Yang

et al. 2020

Front. Cell Dev. Biol.

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Fatty acid translocase CD36 (CD36) plays an important role in the initiation and pathogenesis of chronic liver disease and non-alcoholic fatty liver disease (NAFLD). The purpose of this study is to investigate the regulation of microRNA-20a-5p (miR-20a-5p) on CD36 in the pathogenesis of NAFLD. Human plasma samples were obtained from NAFLD patients and healthy controls. Mice were fed with high-fat diet to induce an in vivo NAFLD model. Histology staining was performed to examine the morphology and lipid deposition of mouse liver tissue. Real-time PCR, dual-luciferase assay, and western blotting were employed to detect the relationship between miR-20a-5p and CD36. The expression level of miR-20a-5p was decreased in NAFLD patients, HFD mice, and free fatty acid (FFA)-treated HepG2 cells or primary mouse hepatocytes, accompanied by increased lipid production in hepatocytes. MiR-20a-5p suppressed the expression of CD36 to reduce lipid accumulation via binding to its 3’-untranslated region (UTR). However, under the condition of interference with CD36, further inhibition of miR-20a-5p would not cause lipid over-accumulation. In this study, we found that miR-20a-5p played a protective role in lipid metabolic disorders of NAFLD by targeting CD36, which indicated the prospect of miR-20a-5p as a biomarker and treatment target for NAFLD.

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Osteoprotegerin Promotes Liver Steatosis by Targeting the ERK–PPAR-γ–CD36 Pathway

Cited by 70 publications

References 53 publications

Association of metabolic syndrome components with circulating levels of cytokine clusters in young women

Association of metabolic syndrome components with circulating levels of cytokine clusters in young women

Pioglitazone Attenuates Experimental Colitis-Associated Hyperalgesia through Improving the Intestinal Barrier Dysfunction

MicroRNA-20a-5p Ameliorates Non-alcoholic Fatty Liver Disease via Inhibiting the Expression of CD36

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