Imperial College London
Alternate

ProfessorWaljitDhillo

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Endocrinology & Metabolism
 
 
 
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Contact

 

+44 (0)20 7594 3487w.dhillo Website

 
 
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Assistant

 

Ms Suzanne Wheeler +44 (0)20 7594 3487

 
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Location

 

6N6ECommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Guzman:2022:10.1172/JCI145889,
author = {Guzman, S and Dragan, M and Kwon, H and de, Oliveira V and Rao, S and Bhatt, V and Kalemba, KM and Shah, A and Rustgi, VK and Wang, H and Bech, PR and Abbara, A and Izzi-Engbeaya, C and Manousou, P and Guo, JY and Guo, GL and Radovick, S and Dhillo, WS and Wondisford, FE and Babwah, AV and Bhattacharya, M},
doi = {10.1172/JCI145889},
journal = {Journal of Clinical Investigation},
pages = {1--20},
title = {Targeting hepatic kisspeptin receptor ameliorates non-alcoholic fatty liver disease in a mouse model.},
url = {http://dx.doi.org/10.1172/JCI145889},
volume = {132},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Nonalcoholic fatty liver disease (NAFLD), the most common liver disease has become a silent worldwide pandemic. The incidence of NAFLD correlates with the rise in obesity, type 2 diabetes and metabolic syndrome. A hallmark feature of NAFLD is excessive hepatic fat accumulation or steatosis, due to dysregulated hepatic fat metabolism which can progress to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Currently, there are no approved pharmacotherapies to treat this disease. Here we have identified that activation of the kisspeptin receptor (KISS1R) signaling pathway has therapeutic effects in NAFLD. Using high fat diet-fed mice, we demonstrated that a deletion of hepatic Kiss1r exacerbated hepatic steatosis. In contrast, enhanced stimulation of KISS1R protected against steatosis in wild-type C57BL/6J mice and decreased fibrosis using a diet-induced mouse model of NASH. Mechanistically, we found that hepatic KISS1R signaling activates the master energy regulator, AMPK, to thereby decrease lipogenesis and progression to NASH. In NAFLD patients and in HFD-fed mice, hepatic KISS1/KISS1R expression and plasma kisspeptin levels were elevated, suggesting a compensatory mechanism to reduce triglyceride synthesis. These findings establish KISS1R as a therapeutic target to treat NASH.
AU  - Guzman,S
AU  - Dragan,M
AU  - Kwon,H
AU  - de,Oliveira V
AU  - Rao,S
AU  - Bhatt,V
AU  - Kalemba,KM
AU  - Shah,A
AU  - Rustgi,VK
AU  - Wang,H
AU  - Bech,PR
AU  - Abbara,A
AU  - Izzi-Engbeaya,C
AU  - Manousou,P
AU  - Guo,JY
AU  - Guo,GL
AU  - Radovick,S
AU  - Dhillo,WS
AU  - Wondisford,FE
AU  - Babwah,AV
AU  - Bhattacharya,M
DO  - 10.1172/JCI145889
EP  - 20
PY  - 2022///
SN  - 0021-9738
SP  - 1
TI  - Targeting hepatic kisspeptin receptor ameliorates non-alcoholic fatty liver disease in a mouse model.
T2  - Journal of Clinical Investigation
UR  - http://dx.doi.org/10.1172/JCI145889
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35349482
UR  - https://www.jci.org/articles/view/145889#version_history
UR  - http://hdl.handle.net/10044/1/96362
VL  - 132
ER  -
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