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Sitagliptin attenuates methionine/choline-deficient diet-induced steatohepatitis

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Author(s)
Yun-A. JungYeon-Kyung ChoiGwon-Soo JungHye-Young SeoHye-Soon KimByoung Kuk JangJung-Guk KimIn-Kyu LeeMi-Kyung KimKeun-Gyu Park
Keimyung Author(s)
Kim, Hye SoonJang, Byoung KukKim, Mi Kyung
Department
Dept. of Internal Medicine (내과학)
Journal Title
Diabetes Research and Clinical Practice
Issued Date
2014
Volume
105
Issue
1
Abstract
Aims: Accumulating evidence suggests that inhibitors of dipeptidyl peptidase-4 (DPP-4),
such as sitagliptin, may play an important role in the prevention of non-alcoholic steato-
hepatitis (NASH). This study was conducted to elucidate whether sitagliptin could prevent
steatohepatitis by inhibiting pathways involved in hepatic steatosis, inflammation, and
fibrosis.
Methods: C57BL/6 mice were fed a methionine/choline-deficient (MCD) diet with or without
supplement with sitagliptin for 5 weeks. Liver and adipose tissue from mice were examined
histologically and immunohistochemically to estimate the effect of sitagliptin on the
development of NASH.
Results: Supplementation with sitagliptin resulted in significant improvement of MCD dietinduced
fat accumulation in the liver. In addition, sitagliptin treatment lowered fatty acid
uptake, expression of VLDL receptor and hepatic triglyceride content. Sitagliptin also
effectively attenuated MCD diet-induced hepatic inflammation, endoplasmic reticulum
(ER) stress, and liver injury, as evidenced by reduced proinflammatory cytokine levels,
ER stress markers, and TUNEL staining. Expression of CYP2E1 and 4NHE were strongly
increased by the MCD diet, but this effect was successfully prevented by sitagliptin treatment.
Furthermore, sitagliptin significantly decreased levels of MCD diet-induced fibrosisassociated
proteins such as fibronectin and a-SMA in the liver. Inflammatory and atrophic
changes of adipose tissue by MCD diet were restored by sitagliptin treatment.
*
Keimyung Author(s)(Kor)
김혜순
장병국
김미경
Publisher
School of Medicine
Citation
Yun-A. Jung et al. (2014). Sitagliptin attenuates methionine/choline-deficient
diet-induced steatohepatitis. Diabetes Research and Clinical Practice, 105(1), 47–57. doi: 10.1016/j.diabres.2014.04.028
Type
Article
ISSN
0168-8227
Source
https://www.sciencedirect.com/science/article/pii/S0168822714002113?via%3Dihub
DOI
10.1016/j.diabres.2014.04.028
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35577
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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