Abstract

Inflammatory bowel disease is defined by inflammation and immune dysregulation. This study investigated the effects of Gα13 liver-specific knockout (LKO) on proximal and distal colons of dextran sodium sulfate (DSS)-induced mice in conjunction with a high-fat diet (HFD). HFD improved body weight gain and disease activity index scores. Gα13LKO exerted no improvement. In the proximal colon, HFD augmented the DSS effect on Il6, which was not observed in Gα13LKO mice. In the distal colon, HFD plus DSS oppositely fortified an increase in Tnfa and Cxcl10 mRNA in Gα13LKO but not WT. Il6 levels remained unchanged. Bioinformatic approaches using Gα13LKO livers displayed bile acid and cholesterol metabolism-related gene sets. Cholic acid and chenodeoxycholic acid levels were increased in the liver of mice treated with DSS, which was reversed by Gα13LKO. Notably, mice treated with DSS showed a reduction in hepatic ABCB11, CYP7B1, CYP7A1, and CYP8B1, which was reversed by Gα13LKO. Overall, feeding HFD augments the effect of DSS on Il6 in the proximal colon of WT, but not Gα13LKO mice, and enhances DSS effect on Tnfa and Cxcl10 in the distal colon of Gα13LKO mice, suggesting site-specific changes in the inflammatory cytokines, potentially resulting from changes in BA synthesis and excretion.

Details

Title
Hepatic Gα13 ablation shifts region-specific colonic inflammatory status by modulating the bile acid synthetic pathway in mice
Author
Kwon, Soon Jae 1 ; Kim, Yun Seok 2 ; Tak, Jihoon 1 ; Lee, Sang Gil 3 ; Lee, Eun Byul 3 ; Kim, Sang Geon 1 

 Dongguk University-Seoul, College of Pharmacy and Integrated Research Institute for Drug Development, Goyang-si, Republic of Korea (GRID:grid.255168.d) (ISNI:0000 0001 0671 5021) 
 Seoul National University College of Medicine, Department of Clinical Pharmacology and Therapeutics, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
 A Pharma Inc., Research and Development Institute, Goyang-si, Republic of Korea (GRID:grid.255168.d) 
Pages
19580
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3096460683
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.