Bile acids regulate anorexigenic neuropeptide through p-STAT3-SOCS3 signaling in mouse hypothalamic cells.
- Author:
Chunxiu CHEN
1
;
Yong ZHOU
2
;
Rongfeng HUANG
3
;
Miaoran WANG
1
;
Yue LI
1
;
Jibin LI
1
Author Information
1. Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing 400016, China.
2. People's Hospital of Banan District, Chongqing 401320, China.
3. Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Cell Line;
Chenodeoxycholic Acid;
pharmacology;
Gene Expression Regulation;
drug effects;
Hypothalamus;
cytology;
Mice;
Neuropeptides;
genetics;
metabolism;
Pro-Opiomelanocortin;
genetics;
RNA, Messenger;
genetics;
STAT3 Transcription Factor;
metabolism;
Signal Transduction;
drug effects;
Suppressor of Cytokine Signaling 3 Protein;
metabolism;
Taurolithocholic Acid;
pharmacology;
alpha-MSH;
genetics
- From:
Journal of Zhejiang University. Medical sciences
2020;40(7):1001-1007
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the effects of taurolithocholic acid (tLCA) and chenodeoxycholic acid (CDCA) on the expression of aorexigenic neuropeptide in mouse hypothalamus GT1-7 cells.
METHODS:Mouse hypothalamic GT1-7 cells were treated with culture medium containing 10% FBS (control group, =3) or with 10 nmol/L, 100 nmol/L, 1 μmol/L and 10 μmol/L tLCA (tLCA group, =3) or CDCA (CDCA group, =3) for 12, 24 or 48 h. Real-time PCR was performed to determine the expression levels of proopiomelanocortin (POMC) mRNA in the cells, and the production levels of α-melanocyte-stimulating hormone (α-MSH) were assessed using an ELISA kit. Signal transduction and activator of transcription 3 phosphorylation (p-STAT3), threonine kinase phosphorylation (p-AKT), suppressor of cytokine signaling 3 (SOCS3), G protein-coupled bile acid receptor-1 (TGR5) and farnesoid X receptor (FXR) protein were detected by Western blotting.
RESULTS:Western blotting results showed that mouse hypothalamic GT1-7 cells expressed two bile acid receptors, TGR5 and FXR, whose expressions were regulated by bile acids. Real-time PCR showed that the expression of POMC mRNA was significantly increased in the cells after treatment with 10 μmol/L tLCA or CDCA for 24 h. POMC-derived anorexigenic peptide α-MSH increased significantly in GT1-7 cells after treatment with 10 μmol/L tLCA or CDCA for 24 h. Treatment of the cells with tLCA or CDCA significantly increased the expressions of intracellular signaling proteins including p-STAT3, p-AKT and SOCS3.
CONCLUSIONS:Mouse hypothalamic GT1-7 cells express bile acid receptors TGR5 and FXR. Bile acids tLCA or CDCA can promote the expression of POMC mRNA and increase the production of the anorexigenic peptide α-MSH. The intracellular signaling proteins p-AKT, p-STAT3 and SOCS3 are likely involved in bile acid-induced anorexigenic peptide production.
