Praziquantel treatment after Schistosoma japonicum infection maintains hepatic insulin sensitivity and improves glucose metabolism in mice

Luo, Xiaofeng; Zhu, Yuxiao; Liu, Ran; Song, Jingwei; Zhang, Fan; Zhang, Wenyue; Zhang, Xu; Hou, Min; Yang, Bo; Chen, Lin; Ji, Minjun

doi:10.1186/s13071-017-2400-5

Cited by 17 publications

(30 citation statements)

References 33 publications

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“…Our previous study showed that the whole-body and hepatic insulin sensitivity were decreased in S. japonicum -infected mice [5]. In consistence with this, the level of fasting blood glucose in mice was significantly decreased after S. japonicum infection (Fig.…”

Section: Resultssupporting

confidence: 57%

“…We previously reported that chronic exposure to S . japonicum induces a type 2 immune response in the liver and improved insulin sensitivity and glucose tolerance [5]. Here, we have further performed in-depth metabolic profiling, which showed that S .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, increasing attention has focused on the inverse association between schistosome infection, the most chronic helminth infections in humans in nature, and metabolism-related diseases, including obesity and diabetes [1, 2]. Recently, several studies have suggested that specific immune responses, such as anti-inflammatory response, eosinophilia and M2 polarization, might contribute at least partly to this issue [3–5]. Importantly, our previous study indicated that chronic S. japonicum infection or SEA treatment in the mouse model can regulate host metabolic homeostasis through promoting Th2 responses in the liver [5].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, several studies have suggested that specific immune responses, such as anti-inflammatory response, eosinophilia and M2 polarization, might contribute at least partly to this issue [3–5]. Importantly, our previous study indicated that chronic S. japonicum infection or SEA treatment in the mouse model can regulate host metabolic homeostasis through promoting Th2 responses in the liver [5]. However, the potential mechanism that regulates the glucose and lipids metabolism of the liver during S. japonicum infection remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver

Zhang

Chang

et al. 2019

Parasites Vectors

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Background Recent investigations indicate that schistosome infection is closely associated with aberrant glycolipid metabolism. However, the actual glycolipid metabolism gene expression, as well as the possible pathways that regulate glycolipid metabolism in the schistosome-infected liver, has not been extensively explored. Methods In this study, we evaluated the dynamic expression of glycolipid metabolism-associated genes and proteins in the livers from mice infected with Schistosoma japonicum at the indicated time points using real-time PCR and immunofluorescence. Then, cultures of macrophages were treated with schistosome soluble egg antigen (SEA) to detect the expression levels of genes associated with glucose and lipid metabolism in order to identify macrophages metabolic characteristics in response to these antigens. Furthermore, SEA-stimulated macrophages were co-cultures with hepatocytes and detected the effects of macrophages on the gene expression of hepatocytes metabolism. Results The expression of glycolysis-related genes (Ldha, Glut4, Pkm2, Glut1, Pfkfb3, Aldoc, HK2, Pfk) in the liver were upregulated but the gluconeogenesis gene (G6pc) was downregulated during S. japonicum infection. In addition, the mRNA levels of fatty acid (FA) oxidation-related genes (Ucp2, Atp5b, Pparg) in the liver were significantly upregulated; however, the FA synthesis genes (Fas, Acc, Scd1, Srebp1c) and lipid uptake gene (Cd36) were downregulated post -S. japonicum -infection. In consistence with these data, stimulation with SEA in vitro significantly enhanced the gene expression that involved in glycolysis and FA oxidation, but decreased genes related to gluconeogenesis, FA synthesis and lipid uptake in macrophages. The levels of phosphorylated AMPK, AKT and mTORC1 were increased in macrophages after SEA stimulation. Inhibition of phosphorylated AMPK, AKT and mTORC1 promoted SEA-treated macrophages to produce glucose. In addition, suppression of phosphorylated-AMPK, but not phosphorylated-AKT and phosphorylated-mTOR, induced the lipid accumulation in SEA-stimulated macrophages. Furthermore, SEA-treated macrophages significantly reduced the expression of Acc mRNA in hepatocytes in vitro . Conclusions These findings reveal S. japonicum infection induces dynamic changes in the expression levels of genes involved in catabolism (glucose uptake, glycolysis and fatty acid oxidation) and suppressing anabolism (glycogen synthesis) in the liver, which could occur via macrophages’ metabolic states, particularly those involved in the AMPK, AKT and mTORC1 pathways. Electronic supplementary material The online version of this article (10.1186/s13071-019-3621-6) contains supplementary material, which is available to auth...

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Section: Resultssupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver

Zhang

Chang

et al. 2019

Parasites Vectors

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“…Hussaarts et al (7) reported that in mice with chronic obesity induced by a high-fat diet, chronic infection with Schistosoma mansoni decreased body weight, fat aggregation, and adipocyte volume and improved adipose tissue sensitivity to insulin in peripheral tissues. Luo et al (8) also reported that chronic S. japonicum infection with praziquantel chemotherapy protected against metabolic syndrome via a mechanism involving the enhancement of the Th2-type immune response. Hams et al (9) reported that ω-1, derived from recombinant S. mansoni eggs, improved the metabolic status of obese mice by the release of the Th2-type cytokine IL-33.…”

Section: Introductionmentioning

confidence: 98%

Schistosoma japonicum Soluble Egg Antigen Protects Against Type 2 Diabetes in Leprdb/db Mice by Enhancing Regulatory T Cells and Th2 Cytokines

Tang

et al. 2019

Front. Immunol.

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Type 2 diabetes is a metabolic disorder characterized by persistently elevated glucose levels. There is no effective treatment strategy for this condition, and it poses a massive economic burden globally. Schistosoma soluble egg antigen (SEA)-induced immunomodulatory mechanisms have been reported in the treatment of autoimmune disease. This study aimed to determine the ability of Schistosoma japonicum SEA to protect against type 2 diabetes in Lep r db / db mice and understand the associated mechanisms. The mice were divided into four groups: C57BL/6 (the normal group), SEA (C57BL/6 mice treated with SEA), Lep r db / db , and SEA and Lep r db / db co-treatment groups. The mice in the SEA and co-treatment groups were injected with 50 μg of SEA (twice a week for 6 weeks), and the same volume of PBS was used as control. Blood glucose, insulin, and HOMA-IR levels were measured in all mice, which were sacrificed 6 weeks after the last SEA administration. Flow cytometry was used to detect the percentages of regulatory T cells in splenocytes. ELISA was used to detect the levels of IFN-γ, IL-2, IL-4, and IL-5 in cell culture supernatants. Compared with the mice in the Lep r db / db group, the mice in the SEA + Lep r db / db group exhibited significantly reduced insulin resistance, as evidenced by the enhancement of wound healing. The frequency of spleen regulatory T cells increased significantly after SEA administration; meanwhile, the secretion of IL-4 and IL-5 in spleen cells was elevated. These results indicate that SEA can reduce insulin resistance and provide new targets for the treatment of type 2 diabetes. The potential mechanisms might be associated with increases in regulatory T cells and Th2 cytokines in Lep r db / db mice, which warrants further investigation.

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The effects of helminth infections against type 2 diabetes

Gao

Zhang

et al. 2021

Parasitol Res

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Praziquantel treatment after Schistosoma japonicum infection maintains hepatic insulin sensitivity and improves glucose metabolism in mice

Cited by 17 publications

References 33 publications

Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver

Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver

Schistosoma japonicum Soluble Egg Antigen Protects Against Type 2 Diabetes in Leprdb/db Mice by Enhancing Regulatory T Cells and Th2 Cytokines

The effects of helminth infections against type 2 diabetes

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