Glycolipid Metabolism Disorder in the Liver of Obese Mice Is Improved by TUDCA via the Restoration of Defective Hepatic Autophagy
Authors: Hongzhi Sun
Bo Zhou
Jiali Liu
Qindong Shi
Shufang Wu
Huixia Li
Qinyue Guo
Journal: International journal of endocrinology (2015)
Discipline: CLINICAL MEDICINE
Keywords: Tauroursodeoxycholic acid; TUDCA; obesity; insulin resistance; autophagic dysfunction
Affiliations: Critical Care Medicine, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, Shaanxi 710061, China., Key Laboratory of Environment and Genes Related to Diseases, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China., Center for Translational Medicine, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, Shaanxi 710061, China., Department of Respiratory, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, Shaanxi 710061, China.

Abstract:  Objective. Tauroursodeoxycholic acid (TUDCA) has been considered an important regulator of energy metabolism in obesity. However, the mechanism underlying how TUDCA is involved in insulin resistance is not fully understood. We tested the effects of TUDCA on autophagic dysfunction in obese mice. Material and Methods. 500 mg/kg of TUDCA was injected into obese mice, and metabolic parameters, autophagy markers, and insulin signaling molecular were assessed by Western blotting and real-time PCR. Results. The TUDCA injections in the obese mice resulted in a reduced body weight gain, lower blood glucose, and improved insulin sensitivity compared with obese mice that were injected with vehicle. Meanwhile, TUDCA treatment not only reversed autophagic dysfunction and endoplasmic reticulum stress, but also improved the impaired insulin signaling in the liver of obese mice. Additionally, the same results obtained with TUDCA were evident in obese mice treated with the adenoviral Atg7. Conclusions. We found that TUDCA reversed abnormal autophagy, reduced ER stress, and restored insulin sensitivity in the liver of obese mice and that glycolipid metabolism disorder was also improved via the restoration of defective hepatic autophagy. 

Retracted: Yes

PubPeer comments:
 ![file] The GAPDH bands have 9 columns, however, other protein samples have 8 columns. , 
 Figures 4 and 5. * Marked in red: The ND Veh panel in Figure 4C appears to show an overlap with the Ad-GFP panel in Figure 5C. Could the authors please clarify if these are the same samples? ![file] , 
 Figure 2G and 4B. * Marked in orange: three lanes in the IL-6 panel of Figure 2G look similar to three lanes in the p-eIF2a panel in Figure 4B. However, the 4th lanes of both panels is different. ![file] , 
 Figures 4D, 5C, and 5E. * Marked in aqua, blue, and pink: several lanes representing different proteins and experiments look similar, albeit rotated or mirrored, and sometimes with different adjacent lanes. ![file] , 
 Retracted [28 December 2020] . --------------------------------- The article u201cGlycolipid Metabolism Disorder in the Liver of Obese Mice Is Improved by TUDCA via the Restoration of Defective Hepatic Autophagyu201d [1] has been retracted as it was found to contain duplicated figures. As raised on PubPeer [2], there are concerns with Figures 2, 4, and 5. Details of the concerns are as follows: - (i)tIn Figure 2(g), the lanes for IL-6 are similar to the lanes in Figure 4(e) for p-eIF2alpha; - (ii)tIn Figure 4(g), the GAPDH bands have nine lanes; however, the other samples have eight lanes; - (iii)tFigure 4(c) ND Veh overlaps on the left-hand side with the right-hand side of Figure 5(c) Ad-GFP; - (iv)tIn Figures 4(d), 5(c), and 5(e), several bands are duplicated: the left-hand three bands in Figure 5(e) eIF2alpha are highly similar to the right-hand three bands in Figure 5(g) Akt, bands 2u20134 in Figure 4(e) IR when mirrored horizontally, and the right-hand three bands in Figure 5(g) IR when flipped vertically. Lane 5 in Figure 5(g) Akt is also highly similar to lane 5 in Figure 5(g) IR when flipped vertically. The right-hand seven bands in Figure 4(e) IR are highly similar to the right-hand seven bands in Figure 5(g) IR when flipped. We asked the authors to explain this and provide the underlying images and raw data for all the figures. They said that the GAPDH bands in Figure 4, ND Veh in Figure 4, and Ad-GFP in Figure 5 are all control samples and the photos might have been mistakenly selected but would not affect the conclusion of the article, and that the other bands were not duplicated. Given the extent of the issues identified, the editorial board recommended retracting the article. The authors do not agree with retraction. -------------------------------- Assessed here, as part of the third of 10 broad investigations: https: www.nsfc.gov.cn publish portal0 tab442 info85495.htm **Decisions on handling scientific research misconduct cases investigated and dealt with in 2022 (first batch)** Date 2022-05-13 Source: u3000 Author: u3000 u3010 Large, Middle and Small u3011 u3010Printu3011 u3010Closeu3011 u3000u3000The National Natural Science Foundation of China resolutely implements the spirit of the  Several Opinions on Further Strengthening the Construction of Scientific Research Integrity and  Opinions on Further Promoting the Spirit of Scientists and Strengthening the Construction of Style and Study Style by the General Office of the Central Committee of the Communist Party of China and the General Office of the State Council. Horizontal science and technology are self-reliant and self-reliant, continue to carry out scientific research integrity construction, and seriously investigate and deal with scientific research misconduct involving the National Natural Science Foundation of China. The Supervision Committee of the National Natural Science Foundation of China conducts investigations, verifications and comprehensive judgments on the accepted scientific research integrity cases, in accordance with the Regulations of the National Natural Science Foundation of ) and  Measures for Investigation and Handling of Scientific Research Misconduct in National Natural Science Foundation of China and other regulations and systems to propose handling suggestions. After deliberation at the second executive meeting of the National Natural Science Foundation of China in 2022, it was decided to deal with the relevant parties involved. The 10 handling decisions (online release version) that have been criticized and criticized are hereby announced. -------------------------------- **Decision on the handling of problems such as improper image manipulation, confusion of experimental data, and false information in project applications published by Wu Shufang, Zhou Bo, etc.** - National Science and Technology Financial Supervisory Office [2022] No. 11 u3000u3000The Supervision Committee of the National Natural Science Foundation of China launched an investigation into the papers published by Wu Shufang and Zhou Bo of Xi an Jiaotong University for suspected academic misconduct. The papers involved are as follows: ... u3000u3000Paper 4:  QinyueGuo, Qindong Shi, Huixia Li, Jiali Liu, ShufangWu, HongzhiSun, Bo Zhou*. **Glycolipid Metabolism Disorder in the Liver of ObeseMice Is Improved by TUDCA via the Restoration of Defective HepaticAutophagy**. Int J Endocrinol, 2015:687938. u201d (marked with fund numbers 81460287, 81472038, 81500016) ... u3000u3000After investigation, papers 1, 2, and 3 have problems such as improper operation of pictures and confusion of experimental data, and the first author Wu Shufang is mainly responsible. In addition, Wu Shufang listed 3 papers in her application for the National Natural Science Foundation of China (approval numbers 81071440, 81222026, 81472038, 81672221, 81871813) for many times, and she is also responsible for the objective results of false information in the project application; Papers 4 and 5 have problems such as improper operation of pictures and confusion of experimental data. Zhou Bo (the corresponding author of paper 4 and the first author of paper 5) is mainly responsible. In addition, Zhou Bo listed Paper 4 in his final report of the National Natural Science Foundation of China (Grant No. 81500016), and listed Paper 5 in his application for the National Natural Science Foundation of China (Grant No. 81500016), and should also be included in the project application Responsible for the objective results of false information in the book and final report. u3000u3000After deliberation at the 12th meeting of the Fifth National Natural Science Foundation of Item 2 of Article 16 and Item 3 of Article 17,  Measures for Handling Misconduct in Funding Work (for Trial Implementation) , and the revocation of the Wu Shufang National Natural Science Foundation project  FGF21 Mediates  Growth Hormone Insensitivity Cartilage Development  Research on the mechanism of retardation (Grant No. 81071440),  Research on the mechanism of autophagy regulation in cartilage dysfunction-related diseases (Grant No. 81222026),  Research on the mechanism of abnormal cartilage function in the state of growth hormone insensitivity due to peripheral circadian clock disorders (Approval No. 81472038),  Study on the regulation mechanism of Sirt1 on endochondral osteogenesis and maintenance of cartilage homeostasis (Approval No. 81672221),  Study on the direct effect and mechanism of peripheral neurotransmitter NPY in cartilage degeneration (Approval No. 81871813 ), recover the funds allocated for the above 5 projects, cancel Wu Shufangu2019s application qualification for the National Natural Science Foundation of China for 3 years (January 18, 2022 to January 17, 2025), and give Wu Shufang a notice of criticism; Item 4 of Article 35 of the Regulations of the Natural Science Foundation of China, Item 2 of Article 16 and Article 17 of the Measures for Handling Misconduct in the Funding Work of the National Natural Science Foundation of China (for Trial Implementation) The third item is to cancel the Zhou Bo National Natural Science Foundation project  Research on the regulatory mechanism of autophagy in the improvement of airway inflammation in bronchial asthma by chemical partners (Grant No. 81500016), recover the allocated funds, and cancel the Zhou Bo National Natural Science Foundation project Eligibility to apply for 2 years (January 18, 2022 to January 17, 2024), give Zhou Bo a bulletin for criticism. - National Natural Science Foundation of China - March 30, 2022 ,