Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice
| Autor: | Okubo, H., Kushiyama, A., Sakoda, H., Nakatsu, Y., Iizuka, M., Taki, N., Fujishiro, M., Fukushima, Toshiaki, Kamata, H., Nagamachi, A., Inaba, T., Nishimura, F., Katagiri, H., Asahara, T., Yoshida, Y., Chonan, O., Encinas, J., Asano, T. |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Transcription Genetic Lipopolysaccharide Colon Kupffer Cells Biology Gut flora digestive system Article Mice 03 medical and health sciences chemistry.chemical_compound Methionine Immune system Non-alcoholic Fatty Liver Disease Internal medicine medicine Animals Mice Knockout Multidisciplinary Macrophages Methionine choline deficient diet nutritional and metabolic diseases Non alcoholic biology.organism_classification medicine.disease digestive system diseases Choline Deficiency Diet Gastrointestinal Microbiome Lactic acid Toll-Like Receptor 4 Disease Models Animal 030104 developmental biology Endocrinology Gene Expression Regulation Liver chemistry Hormones Ectopic Immunology Intercellular Signaling Peptides and Proteins Resistin Steatohepatitis Biomarkers |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep20157 |
| Popis: | Resistin-like molecule β (RELMβ) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMβ to non-alcoholic steatohepatitis (NASH) development. First, RELMβ knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELMβ and that RELMβ expression levels in the colon and the numbers of RELMβ-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMβ-KO mice to distinguish between the contributions of RELMβ in these two organs. These experiments revealed the requirement of RELMβ in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELMβ-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELMβ in the gut and Kupffer cells to NASH development, raising the possibility of RELMβ being a novel therapeutic target for NASH. |
| Databáze: | OpenAIRE |
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