Adiponectin Modulates DCA-Induced Inflammation via the ROS/NF-Kappa B Signaling Pathway in Esophageal Adenocarcinoma Cells

Zhang, Rong; Yin, Xiaonan; Shi, Haitao; Wu, Jie; Shakya, Pramod; Liu, Dong; Zhang, Jun

doi:10.1007/s10620-013-2877-5

Cited by 24 publications

(19 citation statements)

References 41 publications

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“…Interestingly, adiponectin also directly regulates bile acid homeostasis-related genes such as Cyp7a1 (28). Moreover, adiponectin is capable of alleviating toxic bile deoxycholic acidinduced inflammation in esophageal adenocarcinoma cells (53). In this scenario, it is possible that elevated adiponectin in the ethanol-fed mNTKO mice might directly or indirectly via up-regulation of ileum Fgf15 ameliorate the ethanol-mediated perturbation of bile acid homeostasis, and alleviate liver injury.…”

Section: Discussionmentioning

confidence: 99%

MitoNEET Deficiency Alleviates Experimental Alcoholic Steatohepatitis in Mice by Stimulating Endocrine Adiponectin-Fgf15 Axis

Jogasuria

Wang

et al. 2016

Journal of Biological Chemistry

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MitoNEET (mNT) (CDGSH iron-sulfur domain-containing protein 1 or CISD1) is an outer mitochondrial membrane protein that donates 2Fe-2S clusters to apo-acceptor proteins. In the present study, using a global mNT knock-out (mNTKO) mouse model, we investigated the in vivo functional role of mNT in the development of alcoholic steatohepatitis. Experimental alcoholic steatohepatitis was achieved by pair feeding wild-type (WT) and mNTKO mice with Lieber-DeCarli ethanol-containing diets for 4 weeks. Strikingly, chronically ethanol-fed mNTKO mice were completely resistant to ethanolinduced steatohepatitis as revealed by dramatically reduced hepatic triglycerides, decreased hepatic cholesterol level, diminished liver inflammatory response, and normalized serum ALT levels. Mechanistic studies demonstrated that ethanol administration to mNTKO mice induced two pivotal endocrine hormones, namely, adipose-derived adiponectin and gut-derived fibroblast growth factor 15 (Fgf15). The elevation in circulating levels of adiponectin and Fgf15 led to normalized hepatic and serum levels of bile acids, limited hepatic accumulation of toxic bile, attenuated inflammation, and amelioration of liver injury in the ethanol-fed mNTKO mice. Other potential mechanisms such as reduced oxidative stress, activated Sirt1 signaling, and diminished NF-B activity also contribute to hepatic improvement in the ethanol-fed mNTKO mice. In conclusion, the present study identified adiponectin and Fgf15 as pivotal adipose-gut-liver metabolic coordinators in mediating the protective action of mNT deficiency against development of alcoholic steatohepatitis in mice. Our findings may help to establish mNT as a novel therapeutic target and pharmacological inhibition of mNT may be beneficial for the prevention and treatment of human alcoholic steatohepatitis.NEET proteins (mitoNEET (CISD1, mNT), 3 nutrient-deprivation autophagy factor-1 (NAF-1; CISD2), and Miner 2 (CISD3)) are a class of redox active iron-sulfur (2Fe-2S) proteins (1, 2). Among the three NEET family members, mNT encoded by the CISD1 gene is the founding member of the NEET family, and it is localized in the outer mitochondrial membrane and regulates the maturation and shuttling of 2Fe-2S clusters. mNT has been identified as a mitochondrial target of the anti-diabetic thiazolidinedione drugs (3, 4). Thiazolidinediones such as pioglitazone are capable of binding and stabilizing the mNT protein against 2Fe-2S cluster release, and thus, protecting tissue from mitochondrial injury (4). NAF-1 encoded by CISD2 is closely related to mNT, sharing 44% overall sequence identity and highly similar structure and functions (1, 5). However, the functions of CISD3 are not well understood.Increasing evidences have revealed that mNT is an important regulator of diverse biological processes, including mitochondrial function, iron metabolism, reactive oxygen species (ROS) homeostasis, lipid metabolism, inflammation process, and autophagy (1-4, 6 -15). Utilizing gain and loss of function mouse models, studies have demo...

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Section: Discussionmentioning

confidence: 99%

MitoNEET Deficiency Alleviates Experimental Alcoholic Steatohepatitis in Mice by Stimulating Endocrine Adiponectin-Fgf15 Axis

Jogasuria

Wang

et al. 2016

Journal of Biological Chemistry

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“…52 Furthermore, adiponectin is capable of alleviating inflammation induced by toxic bile acids, such as deoxycholic acid, in esophageal adenocarcinoma cells. 53 …”

Section: Adiponectin-fgf15/19 Signaling Normalizes Bile Acid Homeostasismentioning

confidence: 99%

Endocrine Adiponectin‐FGF15/19 Axis in Ethanol-Induced Inflammation and Alcoholic Liver Injury

et al. 2018

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Alcoholic liver disease (ALD) is the most prevalent form of liver diseases, encompassing a spectrum of progressive pathological changes from steatosis to steatohepatitis to fibrosis/cirrhosis and hepatocellular carcinoma. Alcoholic steatosis/steatohepatitis is the initial stage of ALD and a major risk factor for advanced liver injuries. Adiponectin is a hormone secreted from adipocytes. Fibroblast growth factor (FGF) 15 (human homolog, FGF19) is an ileum-derived hormone. Adipocyte-derived adiponectin and gut-derived FGF15/19 regulate each other, share common signaling cascades and exert similar beneficial functions. Emerging evidence has revealed that dysregulated adiponecitn-FGF15/19 axis and impaired hepatic adiponectin-FGF15/19 signaling are associated with alcoholic liver damage in rodents and humans. More importantly, endocrine adiponectin-FGF15/19 signaling confers protection against ethanol-induced liver damage via fine-tuning the adipose-intestine-liver crosstalk, leading to limited hepatic inflammatory responses, and ameliorated alcoholic liver injury. This review is focused on the recently discovered endocrine adiponectin-FGF15/19 axis that is emerging as an essential adipose-gut-liver coordinator involved in the development and progression of alcoholic steatohepatitis.

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“…NF-κB can be activated by oxidative stress and inflammation, but on the other hand, activation of NF-κB up-regulates the genes modulating oxidative stress, inflammation, cell proliferation, and apoptosis, providing a feedback control [55]. Therefore, activation of NF- kB plays an essential role in the pathogenesis of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Alpha-Lipoic Acid Protects Human Aortic Endothelial Cells Against H2O2-Induced Injury and Inhibits Atherosclerosis in Ovariectomized Low Density Lipoprotein Receptor Knock-Out Mice

Shen

Tian

Shen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Diseases caused by atherosclerosis are the leading causes of death in postmenopausal women, owing to the loss of estradiol. Hormone replacement therapy (HRT) provides short-term beneficial effects in the treatment of cardiovascular disease for postmenopausal women but may increase the risk of stroke and gynecological cancer. Therefore, a substitute for HRT is urgently in needed. Methods: In this study, we examined the effectiveness of alpha-lipoic acid (ALA), a natural potent antioxidant, in preventing the development and progression of atherosclerosis in the low density lipoprotein receptor deficient (Ldlr-/-) mouse model, using western blot analysis, immunohistochemistry, Oil-red-O, elastin staining and TUNEL assay. We also examined the protective effect of ALA in human aortic endothelial cells (HAECs) against H₂O₂-induced oxidative injury, using western blotting, immunofluorescence staining, and monocyte adhesion assay. Results: We showed that ALA treatment significantly reduced the atherosclerosis induced by ovariectomy and high fat diet in the Ldlr-/- mouse model and restored expression of estrogen receptors (ERα and ERβ), which reduced the progression of atherosclerosis. Moreover, ALA treatment attenuated monocyte adhesion, suppressed cellular apoptosis, and eliminated excessive generation of intracellular reactive oxygen species (ROS) by reducing the protein levels of ROS-generating enzymes Nox4 and p22phox, as well as inhibiting NF-κB activation in HAECs stimulated by H₂O₂. Conclusions: ALA could provide a potential treatment for atherosclerosis in postmenopausal patients.

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Adiponectin Modulates DCA-Induced Inflammation via the ROS/NF-Kappa B Signaling Pathway in Esophageal Adenocarcinoma Cells

Abstract: DCA has a pro-inflammatory effect in EAC. f-Ad has an anti-inflammatory effect whereas g-Ad seems to have a pro-inflammatory effect in an ROS/NF-κB p65-dependent manner. This indicates that f-Ad could be a potential anti-inflammatory reagent for cancer therapy.

Cited by 24 publications

References 41 publications

MitoNEET Deficiency Alleviates Experimental Alcoholic Steatohepatitis in Mice by Stimulating Endocrine Adiponectin-Fgf15 Axis

MitoNEET Deficiency Alleviates Experimental Alcoholic Steatohepatitis in Mice by Stimulating Endocrine Adiponectin-Fgf15 Axis

Endocrine Adiponectin‐FGF15/19 Axis in Ethanol-Induced Inflammation and Alcoholic Liver Injury

Alpha-Lipoic Acid Protects Human Aortic Endothelial Cells Against H2O2-Induced Injury and Inhibits Atherosclerosis in Ovariectomized Low Density Lipoprotein Receptor Knock-Out Mice

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