Inflammasome-Mediated Cytokines: A Key Connection between Obesity-Associated NASH and Liver Cancer Progression

Cruz, Nathalia Soares da; Pasquarelli-do-Nascimento, Gabriel; Oliveira, Augusto Cézar Polveiro e; Magalhães, Kelly Grace

doi:10.3390/biomedicines10102344

Cited by 7 publications

(5 citation statements)

References 124 publications

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“…Cytokine signaling in obesity-associated NASH is strongly associated with liver cancer progression [ 31 ]. To further elucidate the reason behind the TNF-α- and TGF-β-mediated blockage of IL-6 induced PLIN5 upregulation (cf.…”

Section: Resultsmentioning

confidence: 99%

Lipid-Independent Regulation of PLIN5 via IL-6 through the JAK/STAT3 Axis in Hep3B Cells

Krizanac

Sanchez

Schröder

et al. 2023

IJMS

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Perilipin 5 (PLIN5) is a lipid droplet coat protein that is highly expressed in oxidative tissues such as those of muscles, the heart and the liver. PLIN5 expression is regulated by a family of peroxisome proliferator-activated receptors (PPARs) and modulated by the cellular lipid status. So far, research has focused on the role of PLIN5 in the context of non-alcoholic fatty liver disease (NAFLD) and specifically in lipid droplet formation and lipolysis, where PLIN5 serves as a regulator of lipid metabolism. In addition, there are only limited studies connecting PLIN5 to hepatocellular carcinoma (HCC), where PLIN5 expression is proven to be upregulated in hepatic tissue. Considering that HCC development is highly driven by cytokines present throughout NAFLD development and in the tumor microenvironment, we here explore the possible regulation of PLIN5 by cytokines known to be involved in HCC and NAFLD progression. We demonstrate that PLIN5 expression is strongly induced by interleukin-6 (IL-6) in a dose- and time-dependent manner in Hep3B cells. Moreover, IL-6-dependent PLIN5 upregulation is mediated by the JAK/STAT3 signaling pathway, which can be blocked by transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α). Furthermore, IL-6-mediated PLIN5 upregulation changes when IL-6 trans-signaling is stimulated through the addition of soluble IL-6R. In sum, this study sheds light on lipid-independent regulation of PLIN5 expression in the liver, making PLIN5 a crucial target for NAFLD-induced HCC.

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Section: Resultsmentioning

confidence: 99%

Lipid-Independent Regulation of PLIN5 via IL-6 through the JAK/STAT3 Axis in Hep3B Cells

Krizanac

Sanchez

Schröder

et al. 2023

IJMS

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“…TGF-β is anti-inflammatory and involved in inhibiting apoptosis, while TNF-α, IL-8, FGF-2, and VEGF are involved in hepatic injury or cirrhosis through cell proliferative and angiogenic activities 16,36 . High levels of IL-6 and MCP-1 correlate with worse prognosis for cirrhotic and HCC patients hence suggested as biomarkers to track the development of HCC [37][38][39] . This implies that the low levels of IL-6 and MCP-1 in the HIV+ participants compared to the HCC individuals, could be monitored for liver prognosis.…”

Section: Discussionmentioning

confidence: 99%

Concordance of Cancer-Associated Cytokines and Mitochondrial DNA Deletion Mutations between Individuals with Hepatocellular Carcinoma and People Living with HIV

Aboagye,

Ayanful-Torgby,

Zhou

et al. 2023

Preprint

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Hepatocellular carcinoma (HCC) is a non-AIDS-defining cancer closely tied to the chronic HIV infection and associated with the release of inflammatory cytokines, immune system dysfunction, and genetic alterations within mitochondria. However, our understanding of how these factors contribute to HCC risk in PLWH is limited. The objective of the study was to ascertain the differential secretion of cytokines and mitochondria DNA (mtDNA) deletion in PLWH, and individuals diagnosed with HCC without HIV. A cross-sectional study was conducted with PLWH and HCC participants from the Korle-Bu Teaching Hospital. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated from whole blood. The plasma samples were used to measure cytokines using ELISA and Luminex techniques. We determined mtDNA deletions from PBMCs. We found that the secretion of the cytokines TGF-β, FGF-2, IL-8, TNF-α, VEGF, and RANTES implicated in the pre-cancer, initiation, and early stages of HCC were similar in PLWH compared to HCC participants without HIV. PBMCs of PLWH exhibited high mtDNA deletion (60%) comparable to HCC participants without HIV (64%). These findings underscore the underlying risks associated with HCC development in PLWH. There is a need for HCC surveillance among PLWH and these cytokines could be used as biomarkers.

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“…Both the first and third articles emphasized inter-kingdom signaling, which refers to the interaction between gut bacteria and the host system, and suggested using gut microbiota as a clinical marker for diagnosing, grading, and treating NAFLD. The second article emphasized the link between gut microbiome composition and obesity which is associated with an increased risk of developing NAFLD and liver cancer progression [63,64]. The article of Mouzaki M et al, published by Hepatology in 2013 [54], is in the 10th position in the top 10 most-cited references and also in the top 10 cited articles (Table 4).…”

Section: Analysis Of Co-citation Referencesmentioning

confidence: 99%

Gut Microbiome in the Progression of NAFLD, NASH and Cirrhosis, and Its Connection with Biotics: A Bibliometric Study Using Dimensions Scientific Research Database

Pezzino

Sofia

Mazzone

et al. 2023

Biology

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There is growing evidence that gut microbiota dysbiosis is linked to the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), from the initial stage of disease until the progressive stage of nonalcoholic steatohepatitis (NASH) and the final stage of cirrhosis. Conversely, probiotics, prebiotics, and synbiotics have shown promise in restoring dysbiosis and lowering clinical indicators of disease in a number of both preclinical and clinical studies. Additionally, postbiotics and parabiotics have recently garnered some attention. The purpose of this bibliometric analysis is to assess recent publishing trends concerning the role of the gut microbiome in the progression of NAFLD, NASH and cirrhosis and its connection with biotics. The free access version of the Dimensions scientific research database was used to find publications in this field from 2002 to 2022. VOSviewer and Dimensions’ integrated tools were used to analyze current research trends. Research into the following topics is expected to emerge in this field: (1) evaluation of risk factors which are correlated with the progression of NAFLD, such as obesity and metabolic syndrome; (2) pathogenic mechanisms, such as liver inflammation through toll-like receptors activation, or alteration of short-chain fatty acids metabolisms, which contribute to NAFLD development and its progression in more severe forms, such as cirrhosis; (3) therapy for cirrhosis through dysbiosis reduction, and research on hepatic encephalopathy a common consequence of cirrhosis; (4) evaluation of diversity, and composition of gut microbiome under NAFLD, and as it varies under NASH and cirrhosis by rRNA gene sequencing, a tool which can also be used for the development of new probiotics and explore into the impact of biotics on the gut microbiome; (5) treatments to reduce dysbiosis with new probiotics, such as Akkermansia, or with fecal microbiome transplantation.

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Inflammasome-Mediated Cytokines: A Key Connection between Obesity-Associated NASH and Liver Cancer Progression

Cited by 7 publications

References 124 publications

Lipid-Independent Regulation of PLIN5 via IL-6 through the JAK/STAT3 Axis in Hep3B Cells

Lipid-Independent Regulation of PLIN5 via IL-6 through the JAK/STAT3 Axis in Hep3B Cells

Concordance of Cancer-Associated Cytokines and Mitochondrial DNA Deletion Mutations between Individuals with Hepatocellular Carcinoma and People Living with HIV

Gut Microbiome in the Progression of NAFLD, NASH and Cirrhosis, and Its Connection with Biotics: A Bibliometric Study Using Dimensions Scientific Research Database

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