Spexin Acts as Novel Regulator for Bile Acid Synthesis
Spexin is a novel hormone involved in obesity and diabetes while its biofunctional significance in lipid metabolism is still to be comprehended. Global metabolomic analysis in the present study revealed multiple metabolic pathways altered by spexin intraperitoneal (i.p.) injection in rat serum, whic...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-04-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2018.00378/full |
| _version_ | 1818137424426958848 |
|---|---|
| author | Cheng-yuan Lin Cheng-yuan Lin Ling Zhao Tao Huang Lin Lu Mahjabin Khan Jie Liu Linda L. D. Zhong Zong-wei Cai Bao-min Fan Anderson O. L. Wong Zhao-xiang Bian Zhao-xiang Bian |
| author_facet | Cheng-yuan Lin Cheng-yuan Lin Ling Zhao Tao Huang Lin Lu Mahjabin Khan Jie Liu Linda L. D. Zhong Zong-wei Cai Bao-min Fan Anderson O. L. Wong Zhao-xiang Bian Zhao-xiang Bian |
| author_sort | Cheng-yuan Lin |
| collection | DOAJ |
| description | Spexin is a novel hormone involved in obesity and diabetes while its biofunctional significance in lipid metabolism is still to be comprehended. Global metabolomic analysis in the present study revealed multiple metabolic pathways altered by spexin intraperitoneal (i.p.) injection in rat serum, which are highlighted by the changes in several bile acid metabolites. In rats, spexin (300 μg/kg) could dramatically reduce hepatic and circulating total bile acids (TBA) level compared with the controls. Correspondingly, treatment with spexin by i.p. injection for 28 days led to significant decrease in serum TBA and gallbladder weight in C57BL/6J mice. In enterohepatic circulation system, spexin effectively reduced TBA levels in mouse liver and gallbladder but not the intestine. Hepatic cholesterol 7α-hydroxylase 1 (CYP7A1) expression, unsurprisingly, was suppressed by spexin injection. Both GALR2 and GALR3 antagonists reversed the inhibitory effects of spexin on concentrations of serum TBA and 7 α-hydroxy-4-cholesten-3-one (C4), and hepatic CYP7A1 expression. Finally, negative correlations were observed between serum spexin and total cholesterol (TC), total bile acid (TBA), tauro-chenodeoxycholate (TCDCA), as well as glycochenodeoxycholate (GCDCA) in 91 healthy volunteers. These findings illuminate the intrinsic importance of spexin in the regulation of bile acid synthesis and metabolism. |
| first_indexed | 2024-12-11T09:56:05Z |
| format | Article |
| id | doaj.art-bddbd6cd02f4454ab30c63a66696c74b |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-11T09:56:05Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-bddbd6cd02f4454ab30c63a66696c74b2022-12-22T01:12:15ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-04-01910.3389/fphys.2018.00378361905Spexin Acts as Novel Regulator for Bile Acid SynthesisCheng-yuan Lin0Cheng-yuan Lin1Ling Zhao2Tao Huang3Lin Lu4Mahjabin Khan5Jie Liu6Linda L. D. Zhong7Zong-wei Cai8Bao-min Fan9Anderson O. L. Wong10Zhao-xiang Bian11Zhao-xiang Bian12Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong KongYMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming, ChinaLab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong KongLab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong KongLab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong KongLab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong KongLab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong KongLab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong KongDepartment of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong KongYMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming, ChinaSchool of Biological Sciences, University of Hong Kong, Hong Kong, ChinaLab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong KongYMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming, ChinaSpexin is a novel hormone involved in obesity and diabetes while its biofunctional significance in lipid metabolism is still to be comprehended. Global metabolomic analysis in the present study revealed multiple metabolic pathways altered by spexin intraperitoneal (i.p.) injection in rat serum, which are highlighted by the changes in several bile acid metabolites. In rats, spexin (300 μg/kg) could dramatically reduce hepatic and circulating total bile acids (TBA) level compared with the controls. Correspondingly, treatment with spexin by i.p. injection for 28 days led to significant decrease in serum TBA and gallbladder weight in C57BL/6J mice. In enterohepatic circulation system, spexin effectively reduced TBA levels in mouse liver and gallbladder but not the intestine. Hepatic cholesterol 7α-hydroxylase 1 (CYP7A1) expression, unsurprisingly, was suppressed by spexin injection. Both GALR2 and GALR3 antagonists reversed the inhibitory effects of spexin on concentrations of serum TBA and 7 α-hydroxy-4-cholesten-3-one (C4), and hepatic CYP7A1 expression. Finally, negative correlations were observed between serum spexin and total cholesterol (TC), total bile acid (TBA), tauro-chenodeoxycholate (TCDCA), as well as glycochenodeoxycholate (GCDCA) in 91 healthy volunteers. These findings illuminate the intrinsic importance of spexin in the regulation of bile acid synthesis and metabolism.http://journal.frontiersin.org/article/10.3389/fphys.2018.00378/fullbile acidCYP7A1spexinultraperformance liquid chromatography mass spectrometrymetabolism |
| spellingShingle | Cheng-yuan Lin Cheng-yuan Lin Ling Zhao Tao Huang Lin Lu Mahjabin Khan Jie Liu Linda L. D. Zhong Zong-wei Cai Bao-min Fan Anderson O. L. Wong Zhao-xiang Bian Zhao-xiang Bian Spexin Acts as Novel Regulator for Bile Acid Synthesis Frontiers in Physiology bile acid CYP7A1 spexin ultraperformance liquid chromatography mass spectrometry metabolism |
| title | Spexin Acts as Novel Regulator for Bile Acid Synthesis |
| title_full | Spexin Acts as Novel Regulator for Bile Acid Synthesis |
| title_fullStr | Spexin Acts as Novel Regulator for Bile Acid Synthesis |
| title_full_unstemmed | Spexin Acts as Novel Regulator for Bile Acid Synthesis |
| title_short | Spexin Acts as Novel Regulator for Bile Acid Synthesis |
| title_sort | spexin acts as novel regulator for bile acid synthesis |
| topic | bile acid CYP7A1 spexin ultraperformance liquid chromatography mass spectrometry metabolism |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2018.00378/full |
| work_keys_str_mv | AT chengyuanlin spexinactsasnovelregulatorforbileacidsynthesis AT chengyuanlin spexinactsasnovelregulatorforbileacidsynthesis AT lingzhao spexinactsasnovelregulatorforbileacidsynthesis AT taohuang spexinactsasnovelregulatorforbileacidsynthesis AT linlu spexinactsasnovelregulatorforbileacidsynthesis AT mahjabinkhan spexinactsasnovelregulatorforbileacidsynthesis AT jieliu spexinactsasnovelregulatorforbileacidsynthesis AT lindaldzhong spexinactsasnovelregulatorforbileacidsynthesis AT zongweicai spexinactsasnovelregulatorforbileacidsynthesis AT baominfan spexinactsasnovelregulatorforbileacidsynthesis AT andersonolwong spexinactsasnovelregulatorforbileacidsynthesis AT zhaoxiangbian spexinactsasnovelregulatorforbileacidsynthesis AT zhaoxiangbian spexinactsasnovelregulatorforbileacidsynthesis |