DJ-1 contributes to adipogenesis and obesity-induced inflammation

Kim, Jungmin; Jang, Hyun‐Jun; Choi, Soo Youn; Park, Soo-Ah; Kim, Il Shin; Yang, Yong Ryoul; Lee, Yong Hwa; Ryu, Sung Ho; Suh, Pann‐Ghill

doi:10.1038/srep04805

Cited by 34 publications

(23 citation statements)

References 43 publications

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“…Although it has not been described, we hypothesize that as occurs with leptin, this adipokine may be increasingly secreted during the development of obesity, and probably part of this secretion occurs through EVs as validated by immunoblot in the present research. Other interesting proteins, related to obesity, were also identified in the pathological vesicles of our analysis such as protein/nucleic acid deglycase DJ-1, involved in adipogenesis and obesity-induced inflammation [47], PPIB, an adipogenic factor implicated in obesity [30], or tenascin, involved in obesity via visceral adipose tissue inflammation representing a link with extracellular matrix (ECM) remodeling [48].…”

Section: Despite the Recent Up Surge Of Extracellular Vesicles Revealmentioning

confidence: 89%

“…Elevated in vesicles from oleic acid hypertrophied adipocytes are other proteins of interest in relation to adipose tissue and obesity, such as PARK7/DJ-1 and MMP-14. DJ-1 protein is implicated in oxidative stress regulation among other functions, but has been also described as participating in adipogenesis and in obesity-induced inflammation [47]. Furthermore, MMP-14 was found to be overexpressed in obese adipose participating in abnormal lipid metabolism and insulin resistance [28].…”

Section: Despite the Recent Up Surge Of Extracellular Vesicles Revealmentioning

confidence: 99%

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Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

Camino

Lago-Baameiro

Bravo

et al. 2020

IJMS

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Extracellular vesicles (EVs) have recently emerged as a relevant way of cell to cell communication, and its analysis has become an indirect approach to assess the cell/tissue of origin status. However, the knowledge about their nature and role on metabolic diseases is still very scarce. We have established an insulin resistant (IR) and two lipid (palmitic/oleic) hypertrophied adipocyte cell models to isolate EVs to perform a protein cargo qualitative and quantitative Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) analysis by mass spectrometry. Our results show a high proportion of obesity and IR-related proteins in pathological EVs; thus, we propose a panel of potential obese adipose tissue EV-biomarkers. Among those, lipid hypertrophied vesicles are characterized by ceruloplasmin, mimecan, and perilipin 1 adipokines, and those from the IR by the striking presence of the adiposity and IR related transforming growth factor-beta-induced protein ig-h3 (TFGBI). Interestingly, functional assays show that IR and hypertrophied adipocytes induce differentiation/hypertrophy and IR in healthy adipocytes through secreted EVs. Finally, we demonstrate that lipid atrophied adipocytes shed EVs promote macrophage inflammation by stimulating IL-6 and TNFα expression. Thus, we conclude that pathological adipocytes release vesicles containing representative protein cargo of the cell of origin that are able to induce metabolic alterations on healthy cells probably exacerbating the disease once established.

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Section: Despite the Recent Up Surge Of Extracellular Vesicles Revealmentioning

confidence: 89%

Section: Despite the Recent Up Surge Of Extracellular Vesicles Revealmentioning

confidence: 99%

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

Camino

Lago-Baameiro

Bravo

et al. 2020

IJMS

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“…It has been shown that DJ‐1 expression is reduced in the pancreatic islets of patients with type II diabetes mellitus (Jain et al ., ). Furthermore, DJ‐1‐deficient mice neurons exhibit a significantly higher sensitivity to energy metabolism impairment compared to controls (Pisani et al ., ), and decreased DJ‐1 expression in 3T3‐L1 cells results in reduced adipogenesis and inflammatory cytokine expression (Kim et al ., ). These studies suggest that there may be a possible link between parkin, PINK1 and DJ‐1 and cellular metabolism, and that defects in pathways associated with metabolism could also potentially lead to PD.…”

Section: Direct and Indirect Interactions Between Parkin Pink1 And Dj‐1mentioning

confidence: 97%

Evidence for a common biological pathway linking three Parkinson's disease‐causing genes: parkin, PINK1 and DJ‐1

Merwe

Dashti

Christoffels

et al. 2015

Eur J of Neuroscience

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Parkinson's disease (PD) is characterised by the loss of dopaminergic neurons in the midbrain. Autosomal recessive, early-onset cases of PD are predominantly caused by mutations in the parkin, PINK1 and DJ-1 genes. Animal and cellular models have verified a direct link between parkin and PINK1, whereby PINK1 phosphorylates and activates parkin at the outer mitochondrial membrane, resulting in removal of dysfunctional mitochondria via mitophagy. Despite the overwhelming evidence for this interaction, few studies have been able to identify a link for DJ-1 with parkin or PINK1. The aim of this review is to summarise the functions of these three proteins, and to analyse the existing evidence for direct and indirect interactions between them. DJ-1 is able to rescue the phenotype of PINK1-knockout Drosophila models, but not of parkin-knockouts, suggesting that DJ-1 may act in a parallel pathway to that of the PINK1/parkin pathway. To further elucidate a commonality between these three proteins, bioinformatics analysis established that Miro (RHOT1) interacts with parkin and PINK1, and HSPA4 interacts with all three proteins. Furthermore, 30 transcription factors were found to be common amongst all three proteins, with many of them being involved in transcriptional regulation. Interestingly, expression of these proteins and their associated transcription factors are found to be significantly down-regulated in PD patients compared to healthy controls. In summary, this review provides insight into common pathways linking three PD-causing genes and highlights some key questions, the answers to which may provide critical insight into the disease process.

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“…Macrophages with DJ-1 deficiency showed downregulation of NF-κB-targeted pro-inflammatory cytokines in vitro . 24 Additionally, our recent study has demonstrated that DJ-1 is a pivotal modulator in triggering inflammatory response by targeting NADPH oxidase-mediated reactive oxygen species (ROS) generation and subsequently enhancing the secretion of pro-inflammatory cytokines, such as IL-6 and TNF- α , which are well known to promote LPC proliferation. 6, 25 However, whether DJ-1 could stimulate LPC proliferation by modulating the inflammatory and fibrosis microenvironment remains elusive.…”

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confidence: 99%

DJ-1 deficiency attenuates expansion of liver progenitor cells through modulating the inflammatory and fibrogenic niches

et al. 2016

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Our previous study suggested that DJ-1 has a critical role in initiating an inflammatory response, but its role in the liver progenitor cell (LPC) expansion, a process highly dependent on the inflammatory niche, remains elusive. The objective of this study is to determine the role of DJ-1 in LPC expansion. The correlation of DJ-1 expression with LPC markers was examined in the liver of patients with hepatitis B or hepatitis C virus (HBV and HCV, respectively) infection, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), nonalcoholic fatty liver disease (NAFLD), cirrhosis or hepatocellular carcinoma (HCC), respectively. The role of DJ-1 in LPC expansion and the formation of LPC-associated fibrosis and inflammation was examined in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-induced liver injury murine model. We also determined the ability of hepatic stellate cells (HSCs) in recruiting macrophages in DJ-1 knockout (KO) mice. The expression levels of DJ-1 were upregulated in the liver of HBV, HCV, PBC and PSC patients and DDC-fed mice. Additionally, DJ-1 expression was positively correlated with LPC proliferation in patients with liver injury and mice with DDC exposure. DJ-1 has no direct effect on LPC proliferation. Reduced activation of HSCs and collagen deposition were observed in DJ-1 KO mice. Furthermore, infiltrated CD11b+Gr-1low macrophages and pro-inflammatory factors (IL-6, TNF-α) were attenuated in DJ-1 KO mice. Mechanistically, we found that HSCs isolated from DJ-1 KO mice had decreased secretion of macrophage-mobilizing chemokines, such as CCL2 and CX3CL1, resulting in impaired macrophage infiltration. DJ-1 positively correlates with LPC expansion during liver injury. DJ-1 deficiency negatively regulates LPC proliferation by impairing the formation of LPC-associated fibrosis and inflammatory niches.

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DJ-1 contributes to adipogenesis and obesity-induced inflammation

Cited by 34 publications

References 43 publications

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

Evidence for a common biological pathway linking three Parkinson's disease‐causing genes: parkin, PINK1 and DJ‐1

DJ-1 deficiency attenuates expansion of liver progenitor cells through modulating the inflammatory and fibrogenic niches

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