Reducing gut microbiome-driven adipose tissue inflammation alleviates metabolic syndrome
Posted on 2023-09-22 - 03:24
Abstract Background 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. Results In this study, we integrated and interrogated multi-omics data from different organs with fecal 16S rRNA 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 reduced levels of inflammation-inducing microbes, such as Oscillibacter valericigenes, that lead to adverse metabolic phenotypes. Furthermore, in vitro validation in macrophage cell lines and in vivo mouse supplementation showed addition of O. valericigenes supernatant induced the expression of metabolic macrophage signature genes that are downregulated by TXN in vivo. Conclusions Our findings establish an important mechanism by which TXN mitigates adverse phenotypic outcomes of diet-induced obesity and metabolic syndrome. TXN primarily reduces the abundance of pro-inflammatory gut microbes that can otherwise promote macrophage-associated inflammation in white adipose tissue. Video Abstract
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Newman, N. K.; Zhang, Y.; Padiadpu, J.; Miranda, C. L.; Magana, A. A.; Wong, C. P.; et al. (2023). Reducing gut microbiome-driven adipose tissue inflammation alleviates metabolic syndrome. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.6847148.v1
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (19)
NN
N. K. Newman
YZ
Y. Zhang
JP
J. Padiadpu
CM
C. L. Miranda
AM
A. A. Magana
CW
C. P. Wong
KH
K. A. Hioki
JP
J. W. Pederson
ZL
Z. Li
MG
M. Gurung
AB
A. M. Bruce
KB
K. Brown
GB
G. Bobe
TS
T. J. Sharpton
NS
N. Shulzhenko
CM
C. S. Maier
JS
J. F. Stevens
AG
A. F. Gombart
AM
A. Morgun
KEYWORDS
transkingdom network analysissynthetic derivative tetrahydroxanthohumolbile acid compositionadverse metabolic phenotypesreducing gut microbiomeotherwise promote macrophagewhite adipose tissuevalericigenes supernatant inducedtxn primarily reducesinflammatory gene expressioninflammatory gut microbesgut microbiota contributesmacrophage cell linesadipose tissuegut microbiotaoscillibacter valericigenesmetabolic syndromeinducing microbesinduced obesitycell rnavitro validationvideo abstractthus drivingseq dataomics datainterrogated multiimportant mechanismfindings establishdifferent organsdevelop interventionsattenuate high6j mice