Mark4 promotes oxidative stress and inflammation via binding to PPARγ and activating NF-κB pathway in mice adipocytes

Liu, Zhenjiang; Gan, Lu; Chen, Yizhe; Luo, Dan; Zhang, Zhenzhen; Cao, Weina; Zhou, Zhongjie; Lin, Xueting; Sun, Cheng

doi:10.1038/srep21382

Cited by 55 publications

(79 citation statements)

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“…Additionally, studies have found that Mark4 promoted oxidative stress and inflammation via binding to the peroxisome proliferator-activated receptor gamma (PPARγ) and activating nuclear factor-kappa B (NF-κB) pathway in mice adipocytes. These data establish a novel regulation role of Mark4 on body metabolic balance [11].…”

Section: Introductionsupporting

confidence: 53%

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Mark4 Inhibited the Browning of White Adipose Tissue by Promoting Adipocytes Autophagy in Mice

Yang

Cai

Pan

et al. 2020

IJMS

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Autophagy can remove excess or dysfunctional proteins and organelles to maintain cellular homeostasis. Browning of white adipose tissue increases the energy expenditure. Microtubules affinity regulated kinase 4 (Mark4) can regulate a variety of physiological processes. According to previous studies, we speculated that Mark4-autophagy-browning of white adipose tissue had certain linkages. Here, we established two autophagy models through serum starvation and rapamycin treatment and detected that the overexpression of Mark4 increased the expression of autophagy-related factors Beclin1, ATG7, and significantly decreased the autophagy substrate P62. Further tests showed that the overexpression of Mark4 promoted the conversion of autophagy marker protein LC3A to LC3B-II by activating the AMP-activated protein kinase (AMPK) pathway and inhibition of the AKT/mTOR signaling. Moreover, Mark4 decreased the expression of thermogenesis genes via promoting autophagy. These results indicated that Mark4 inhibited the browning of white adipose tissue via promoting autophagy. AMPK signaling pathway. By adding compound C, the phosphorylation of AMPK and the formation of LC3B-II were reduced while the level of autophagy substrate p62 was increased ( Figure 4A,B). The results of AKT pathway examination was opposite. The overexpression of Mark4 significantly inhibited the phosphorylation of AKT and mTOR, accompanied by an increase in LC3B-II and a decrease in P62. After treating with the AKT inhibitor MK2206, the phosphorylation levels of AKT, mTOR, and the protein level of P62 were significantly reduced. The LC3B-II expression was increased ( Figure 4C,D). These results indicated that Mark4 could regulate serum starvation-induced autophagy via the AMPK/AKT signal pathway.

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Section: Introductionsupporting

confidence: 53%

“…The activation of the JNK signaling pathway can trigger adipocyte apoptosis [10]. In addition, there are reports that Mark4 promotes oxidative stress and inflammation via binding to PPARγ and activating the NF-κB pathway in mice adipocytes [11]. These data establish novel regulation roles of Mark4 in body metabolic balance.…”

Section: Discussionmentioning

confidence: 90%

Mark4 Inhibited the Browning of White Adipose Tissue by Promoting Adipocytes Autophagy in Mice

Yang

Cai

Pan

et al. 2020

IJMS

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“…While the basis for these metabolic defects have not been fully elucidated, MARK4 is expressed in adipocytes where it has been shown to regulate respiration, proliferation and apoptosis (Feng et al, 2014; Liu et al, 2016). MARK2 knockout mice have a number of other phenotypes, including dwarfism, infertility, reduced learning and memory and immune system dysfunction (Bessone et al, 1999; Hurov et al, 2001; Segu et al, 2008).…”

Section: Structure and Regulation Of Par-1/mark Kinasesmentioning

confidence: 99%

Regulation of Cell Polarity by PAR-1/MARK Kinase

Griffin

2017

Current Topics in Developmental Biology

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PAR-1/MARK kinases are conserved serine/threonine kinases that are essential regulators of cell polarity. PAR-1/MARK kinases localize and function in opposition to the Anterior PAR proteins to control the asymmetric distribution of factors in a wide variety polarized cells. In this review, we discuss the mechanisms that control the localization and activity of PAR-1/MARK kinases, including their antagonistic interactions with the Anterior PAR proteins. We focus on the role PAR-1 plays in the asymmetric division of the C. elegans zygote, in the establishment of the anterior/posterior axis in the Drosophila oocyte and in the control of microtubule dynamics in mammalian neurons. In addition to conserved aspects of PAR-1 biology, we highlight the unique ways in which PAR-1 acts in these distinct cell types to orchestrate their polarization. Finally, we review the connections between disruptions in PAR-1/MARK function and Alzheimer’s disease and cancer.

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“…Mitochondrial DNA copy number percell was quantified as described. Realtime quantitative PCR was carried out using the real-time PCR detection system as previous described [16]. …”

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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Mark4 promotes oxidative stress and inflammation via binding to PPARγ and activating NF-κB pathway in mice adipocytes

Cited by 55 publications

References 50 publications

Mark4 Inhibited the Browning of White Adipose Tissue by Promoting Adipocytes Autophagy in Mice

Mark4 Inhibited the Browning of White Adipose Tissue by Promoting Adipocytes Autophagy in Mice

Regulation of Cell Polarity by PAR-1/MARK Kinase

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

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