Enhancement of Adiponectin Ameliorates Nonalcoholic Fatty Liver Disease via Inhibition of FoxO1 in Type I Diabetic Rats

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease which has been previously shown to be associated with type 2 diabetes mellitus (T2DM). Recent research has indicated that type 1 diabetes mellitus (T1DM) is also involved in the development of nonalcoholic fatty liver disease, wherea...

Full description

Saved in:
Bibliographic Details
Main Authors: Xiang Xie, Dan Yan, Haobo Li, Qiqi Zhu, Jun Li, Yong-ping Fang, Chi Wai Cheung, Michael G. Irwin, Zhengyuan Xia, Qingquan Lian
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2018/6254340
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849691839155666944
author Xiang Xie
Dan Yan
Haobo Li
Qiqi Zhu
Jun Li
Yong-ping Fang
Chi Wai Cheung
Michael G. Irwin
Zhengyuan Xia
Qingquan Lian
author_facet Xiang Xie
Dan Yan
Haobo Li
Qiqi Zhu
Jun Li
Yong-ping Fang
Chi Wai Cheung
Michael G. Irwin
Zhengyuan Xia
Qingquan Lian
author_sort Xiang Xie
collection DOAJ
description Nonalcoholic fatty liver disease (NAFLD) is a common liver disease which has been previously shown to be associated with type 2 diabetes mellitus (T2DM). Recent research has indicated that type 1 diabetes mellitus (T1DM) is also involved in the development of nonalcoholic fatty liver disease, whereas the underlying mechanisms are largely unknown. Forkhead box O1 (FoxO1) and adiponectin (APN) have been proposed to play an important role in the processes in NAFLD in T1DM. We herein investigated the effects of FoxO1 and APN on the development of NAFLD and the underlying mechanism in streptozotocin-induced T1DM. Serum liver enzymes AST, ALT, and triglyceride (TG) were determined by commercially available kits. Blood glucose levels were measured by the OneTouch Ultra glucose meter. Relevant protein expression was tested by Western blot analysis. Results showed that serum AST, ALT, and TG were all significantly increased in T1DM rats, which was ameliorated by application of APN or selective inhibition of FoxO1 with AS1842856. Moreover, APN and AS1842856 both decreased the expression of liver nuclear FoxO1 which was significantly increased in diabetic rats. However, the inhibition of FoxO1 did not alter the expression of APN and its receptors. We also found that Akt1 expression was significantly declined in diabetic rat which was restored by APN and moderately and significantly increased by FoxO1 inhibition. It is concluded that APN ameliorates NAFLD via inhibition of FoxO1 through Akt1/FoxO1 signaling pathway.
format Article
id doaj-art-b65a144ef36e4cfcac7a85ca8ef22f57
institution DOAJ
issn 2314-6745
2314-6753
language English
publishDate 2018-01-01
publisher Wiley
record_format Article
series Journal of Diabetes Research
spelling doaj-art-b65a144ef36e4cfcac7a85ca8ef22f572025-08-20T03:20:54ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/62543406254340Enhancement of Adiponectin Ameliorates Nonalcoholic Fatty Liver Disease via Inhibition of FoxO1 in Type I Diabetic RatsXiang Xie0Dan Yan1Haobo Li2Qiqi Zhu3Jun Li4Yong-ping Fang5Chi Wai Cheung6Michael G. Irwin7Zhengyuan Xia8Qingquan Lian9Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, ChinaDepartment of Anesthesiology, The University of Hong Kong, Pok Fu Lam, Hong KongDepartment of Anesthesiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, ChinaDepartment of General Surgery, Huizhou First Hospital, Huizhou, Guangdong, ChinaDepartment of Anesthesiology, The University of Hong Kong, Pok Fu Lam, Hong KongDepartment of Anesthesiology, The University of Hong Kong, Pok Fu Lam, Hong KongDepartment of Anesthesiology, The University of Hong Kong, Pok Fu Lam, Hong KongDepartment of Anesthesiology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, ChinaNonalcoholic fatty liver disease (NAFLD) is a common liver disease which has been previously shown to be associated with type 2 diabetes mellitus (T2DM). Recent research has indicated that type 1 diabetes mellitus (T1DM) is also involved in the development of nonalcoholic fatty liver disease, whereas the underlying mechanisms are largely unknown. Forkhead box O1 (FoxO1) and adiponectin (APN) have been proposed to play an important role in the processes in NAFLD in T1DM. We herein investigated the effects of FoxO1 and APN on the development of NAFLD and the underlying mechanism in streptozotocin-induced T1DM. Serum liver enzymes AST, ALT, and triglyceride (TG) were determined by commercially available kits. Blood glucose levels were measured by the OneTouch Ultra glucose meter. Relevant protein expression was tested by Western blot analysis. Results showed that serum AST, ALT, and TG were all significantly increased in T1DM rats, which was ameliorated by application of APN or selective inhibition of FoxO1 with AS1842856. Moreover, APN and AS1842856 both decreased the expression of liver nuclear FoxO1 which was significantly increased in diabetic rats. However, the inhibition of FoxO1 did not alter the expression of APN and its receptors. We also found that Akt1 expression was significantly declined in diabetic rat which was restored by APN and moderately and significantly increased by FoxO1 inhibition. It is concluded that APN ameliorates NAFLD via inhibition of FoxO1 through Akt1/FoxO1 signaling pathway.http://dx.doi.org/10.1155/2018/6254340
spellingShingle Xiang Xie
Dan Yan
Haobo Li
Qiqi Zhu
Jun Li
Yong-ping Fang
Chi Wai Cheung
Michael G. Irwin
Zhengyuan Xia
Qingquan Lian
Enhancement of Adiponectin Ameliorates Nonalcoholic Fatty Liver Disease via Inhibition of FoxO1 in Type I Diabetic Rats
Journal of Diabetes Research
title Enhancement of Adiponectin Ameliorates Nonalcoholic Fatty Liver Disease via Inhibition of FoxO1 in Type I Diabetic Rats
title_full Enhancement of Adiponectin Ameliorates Nonalcoholic Fatty Liver Disease via Inhibition of FoxO1 in Type I Diabetic Rats
title_fullStr Enhancement of Adiponectin Ameliorates Nonalcoholic Fatty Liver Disease via Inhibition of FoxO1 in Type I Diabetic Rats
title_full_unstemmed Enhancement of Adiponectin Ameliorates Nonalcoholic Fatty Liver Disease via Inhibition of FoxO1 in Type I Diabetic Rats
title_short Enhancement of Adiponectin Ameliorates Nonalcoholic Fatty Liver Disease via Inhibition of FoxO1 in Type I Diabetic Rats
title_sort enhancement of adiponectin ameliorates nonalcoholic fatty liver disease via inhibition of foxo1 in type i diabetic rats
url http://dx.doi.org/10.1155/2018/6254340
work_keys_str_mv AT xiangxie enhancementofadiponectinamelioratesnonalcoholicfattyliverdiseaseviainhibitionoffoxo1intypeidiabeticrats
AT danyan enhancementofadiponectinamelioratesnonalcoholicfattyliverdiseaseviainhibitionoffoxo1intypeidiabeticrats
AT haoboli enhancementofadiponectinamelioratesnonalcoholicfattyliverdiseaseviainhibitionoffoxo1intypeidiabeticrats
AT qiqizhu enhancementofadiponectinamelioratesnonalcoholicfattyliverdiseaseviainhibitionoffoxo1intypeidiabeticrats
AT junli enhancementofadiponectinamelioratesnonalcoholicfattyliverdiseaseviainhibitionoffoxo1intypeidiabeticrats
AT yongpingfang enhancementofadiponectinamelioratesnonalcoholicfattyliverdiseaseviainhibitionoffoxo1intypeidiabeticrats
AT chiwaicheung enhancementofadiponectinamelioratesnonalcoholicfattyliverdiseaseviainhibitionoffoxo1intypeidiabeticrats
AT michaelgirwin enhancementofadiponectinamelioratesnonalcoholicfattyliverdiseaseviainhibitionoffoxo1intypeidiabeticrats
AT zhengyuanxia enhancementofadiponectinamelioratesnonalcoholicfattyliverdiseaseviainhibitionoffoxo1intypeidiabeticrats
AT qingquanlian enhancementofadiponectinamelioratesnonalcoholicfattyliverdiseaseviainhibitionoffoxo1intypeidiabeticrats