| Autor: |
N. K. Newman, Y. Zhang, J. Padiadpu, C. L. Miranda, A. A. Magana, C.P. Wong, K. A. Hioki, J. W. Pederson, Z. Li, M. Gurung, A. M. Bruce, K Brown, G. Bobe, T. J. Sharpton, N. Shulzhenko, C. S. Maier, J. F. Stevens, A. F. Gombart, A. Morgun |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.10.28.514267 |
| Popis: |
The gut microbiota contributes to macrophage-mediated inflammation in adipose tissue with consumption of an obesogenic diet, thus driving the development of metabolic syndrome. There is a need to identify and develop interventions that abrogate this condition. The hops-derived prenylated flavonoid xanthohumol (XN) and its semi-synthetic derivative tetrahydroxanthohumol (TXN) attenuate high-fat diet-induced obesity, hepatosteatosis and metabolic syndrome in C57Bl/6J mice. This coincides with a decrease in pro-inflammatory gene expression in the gut and adipose tissue, together with alterations in the gut microbiota and bile acid composition. In this study, we integrated and interrogated multi-omics data from different organs with fecal 16S sequences and systemic metabolic phenotypic data using a transkingdom network analysis. By incorporating cell type information from single cell RNA-seq data, we discovered TXN attenuates macrophage inflammatory processes in adipose tissue. TXN treatment also reversed levels of inflammation-inducing microbes, such asOscillibacter valericigenes, that lead to adverse metabolic phenotypes. Furthermore,in vitrovalidation in macrophage cell lines andin vivomouse supplementation showed addition ofO. valericigenessupernatant induced the expression of metabolic macrophage signature genes that are downregulated by TXNin vivo. Our findings establish an important mechanism by which TXN mitigates adverse phenotypic outcomes from diet-induced obesity and metabolic syndrome. It primarily reduces the abundance of pro-inflammatory gut microbes that can otherwise promote macrophage-associated inflammation in adipose tissue. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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