αMSH promotes preadipocyte proliferation by alleviating ER stress-induced leptin resistance and by activating Notch1 signal in mice

Gan, Lu; Liu, Zhenjiang; Wu, Tianjiao; Fu, Feng; Sun, Cheng

doi:10.1016/j.bbadis.2016.10.001

Cited by 16 publications

(15 citation statements)

References 38 publications

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“…Protein from adipocytes was extracted using lysing buffer according to the protocol from Liu et al . Protein concentration was determined using BCA Protein Assay kit (Beyotime Institute of Biotechnology, Nanjing, China).…”

Section: Methodsmentioning

confidence: 99%

Melatonin alleviates inflammasome‐induced pyroptosis through inhibiting NF‐κB/GSDMD signal in mice adipose tissue

Liu

Gan

et al. 2017

Journal of Pineal Research

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Pyroptosis is a proinflammatory form of cell death that is associated with pathogenesis of many chronic inflammatory diseases. Melatonin is substantially reported to possess anti-inflammatory properties by inhibiting inflammasome activation. However, the effects of melatonin on inflammasome-induced pyroptosis in adipocytes remain elusive. Here, we demonstrated that melatonin alleviated lipopolysaccharides (LPS)-induced inflammation and NLRP3 inflammasome formation in mice adipose tissue. The NLRP3 inflammasome-mediated pyroptosis was also inhibited by melatonin in adipocytes. Further analysis revealed that gasdermin D (GSDMD), the key executioner of pyroptosis, was the target for melatonin inhibition of adipocyte pyroptosis. Importantly, we determined that nuclear factor κB (NF-κB) signal was required for the GSDMD-mediated pyroptosis in adipocytes. We also confirmed that melatonin alleviated adipocyte pyroptosis by transcriptional suppression of GSDMD. Moreover, GSDMD physically interacted with interferon regulatory factor 7 (IRF7) and subsequently formed a complex to promote adipocyte pyroptosis. Melatonin also attenuated NLRP3 inflammasome activation and pyroptosis, which was induced by LPS or obesity. In summary, our results demonstrate that melatonin alleviates inflammasome-induced pyroptosis by blocking NF-κB/GSDMD signal in mice adipose tissue. Our data reveal a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response.

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Section: Methodsmentioning

confidence: 99%

Melatonin alleviates inflammasome‐induced pyroptosis through inhibiting NF‐κB/GSDMD signal in mice adipose tissue

Liu

Gan

et al. 2017

Journal of Pineal Research

Self Cite

301

244

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“…PPARγ (Ap0686) was purchased from Bioworld. We used GAPDH as internal control gene, and the experimental procedure was described in our previous reports in detail …”

Section: Methodsmentioning

confidence: 99%

Hoxa5 alleviates obesity‐induced chronic inflammation by reducing ER stress and promoting M2 macrophage polarization in mouse adipose tissue

Cao

Zhang

Feng

et al. 2019

J Cellular Molecular Medi

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Obesity‐induced chronic inflammation is associated with endoplasmic reticulum stress (ERS) in adipocytes and changes in both the number and phenotype of adipose tissue macrophages (ATMs). In addition, ERS enhances macrophage activation. So far, the function of Hoxa5 in obesity‐induced chronic inflammation has been poorly understood. Herein, we demonstrate the importance of the transcription factor, Hoxa5, in determining adipose tissue macrophage (ATM) polarity and ERS. Hoxa5 decreased bodyweight, reduced inflammatory cytokine secretion and corresponded with an increased number of M2 macrophages in the adipose tissue of high‐fat diet (HFD) mice. Transcriptome sequencing data showed that overexpression of Hoxa5 in adipocytes changed expression of endoplasmic reticulum (ER) protein processing‐related genes. Based on transcriptome sequencing data and bioinformatics prediction, we have been suggested that Hoxa5 alleviated inflammatory responses by inhibiting ERS and by activating PPARγ pathway in mouse adipose tissue. Hoxa5 alleviated ERS and inflammatory responses by inhibiting the eIF2α/PERK signalling pathway in adipocytes. Hoxa5 also inhibited chronic inflammation of adipocytes by promoting M2 macrophage polarization. In addition, Hoxa5 transcriptionally activated the PPARγ pathway to promote polarization of M2 macrophages, which in turn alleviated chronic inflammation of adipocytes. Taken together, these results shed light on the mechanisms underlying Hoxa5‐dependent inhibition of obesity‐induced chronic inflammation by reducing ERS and promoting polarization of M2 macrophages. These results suggest that Hoxa5 may be a potential therapeutic target for obesity and other metabolic syndromes.

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“…The pre-adipocytes were infected with overexpression Hoxa5 adenovirus vector (pc-Hoxa5) or adenovirus interference vector of Hoxa5 (sh-Hoxa5) for 48 h at the titer of 1 × 10 9 IFU/mL, and then to induce differentiation [20]. Forced expression plasmid vector of CEBPβ (pc-CEBPβ), forced expression plasmid vector of Fabp4 (pc-Fabp4) and interference vector of Fabp4 (sh-Fabp4) were kept in our lab; and the control plasmid vector was pcDNA3.1-vector.…”

Section: Methodsmentioning

confidence: 99%

Hoxa5 Promotes Adipose Differentiation via Increasing DNA Methylation Level and Inhibiting PKA/HSL Signal Pathway in Mice

Cao

Luo

Saeed

et al. 2018

Cell Physiol Biochem

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Background/Aims: Impaired adipogenesis may be the underlying cause in the development of obesity and type II diabetes. Mechanistically, the family of Homeobox transcription factors is implicated in the regulation of adipocyte fate. Hoxa5 is highly expressed in adipocytes, and its mRNA expression is decreased during differentiation. However, the function of Hoxa5 in adipose tissue has been poorly understood. The aim of this study is to unveil the role of Hoxa5 on adipocyte differentiation and its underlying mechanisms. Methods: Quantitative real-time PCR (qPCR) and western blot were performed to determine Hoxa5 expression in primary adipocytes and in adipose tissues from mice. Lipid accumulation was evaluated by bodipy staining. Dual luciferase assay was applied to explore the transcription factor of Hoxa5 and the transcriptional target gene modulated by Hoxa5. All measurements were performed at least for three times at least. Results: A significant reduction of Hoxa5 expression was observed in adipose tissue of High Fat Diet (HFD) induced obesity mice. We determined Hoxa5 increased adipocytes differentiation and mitochondrial biogenesis in adipocytes in vitro. CEBPβ was determined a transcription factor of Hoxa5 and inhibited methylation level of Hoxa5 by combining on the promoter of Hoxa5. Importantly, we found Fabp4, a known positive regulator of adipocytes differentiation, was transcriptional activation by Hoxa5. In addition, Hoxa5 promotes adipocytes differentiation by inhibiting PKA/HSL pathway. Conclusion: Our study demonstrated the promoting role of Hoxa5 in adipocytes differentiation and therefore bringing a new therapeutic mean to the treatment of obesity and type II diabetes.

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αMSH promotes preadipocyte proliferation by alleviating ER stress-induced leptin resistance and by activating Notch1 signal in mice

Cited by 16 publications

References 38 publications

Melatonin alleviates inflammasome‐induced pyroptosis through inhibiting NF‐κB/GSDMD signal in mice adipose tissue

Melatonin alleviates inflammasome‐induced pyroptosis through inhibiting NF‐κB/GSDMD signal in mice adipose tissue

Hoxa5 alleviates obesity‐induced chronic inflammation by reducing ER stress and promoting M2 macrophage polarization in mouse adipose tissue

Hoxa5 Promotes Adipose Differentiation via Increasing DNA Methylation Level and Inhibiting PKA/HSL Signal Pathway in Mice

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