Increased expression of fibroblast growth factor 21 (FGF21) during chronic undernutrition causes growth hormone insensitivity in chondrocytes by inducing leptin receptor overlapping transcript (LEPROT) and leptin receptor overlapping transcript-like 1 (LEPROTL1) expression
Authors: Julie Dam
Francesco De Luca
Alexei Kharitonenkov
Shufang Wu
Tal Grunwald
Ralf Jockers
Journal: Journal of Biological Chemistry (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Chondrocytes; Chondrogenesis; Fibroblast Growth Factor (FGF); Growth Hormone; Growth Plate
Affiliations: From the Section of Endocrinology and Diabetes, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, Pennsylvania 19134.

Abstract:  During calorie restriction in mice, increased expression of FGF21 causes growth attenuation and growth hormone (GH) insensitivity. Previous evidence also indicates that fasting-associated increased expression of leptin receptor overlapping transcript (LEPROT) and LEPROT-like 1 (LEPROTL1) (two proteins that regulate intracellular protein trafficking) reduces GH receptor cell-surface expression in the liver. Thus, we hypothesized that FGF21 causes GH insensitivity through regulation of LEPROT and/or LEPROTL1 expression. After 4 weeks of food restriction, LEPROT and LEPROTL1 mRNA expression in the liver and in the tibial growth plate of wild-type (WT) mice was increased compared with WT mice fed ad libitum. In Fgf21 knock-out (KO) mice, LEPROT and LEPROTL1 mRNA expression in food-restricted and fed ad libitum was similar, with the exception of a subgroup of food-restricted Fgf21 KO mice treated with recombinant human (rh) FGF21 that experienced increased LEPROT and LEPROTL1 mRNA expression compared with untreated food-restricted Fgf21 KO mice. In cultured growth plate chondrocytes, FGF21 stimulated LEPROT and LEPROTL1 mRNA expression, with such effect being prevented in chondrocytes transfected with FGFR1 siRNA or ERK1 siRNA. In cells transfected with control siRNA, GH increased [(3)H]thymidine incorporation, collagen X, and IGF-1 mRNA expression, with all effects being prevented by rhFGF21. In addition, rhFGF21 decreased (125)I-GH binding. In LEPROT siRNA- and/or LEPROTL1 siRNA-transfected cells, rhFGF21 did not prevent the GH stimulatory effects on thymidine incorporation, collagen X, and IGF-1 expression; furthermore, rhFGF21 did not prevent (125)I-GH binding. Consistent with the effects of rhFGF21, LEPROT overexpression in chondrocytes resulted in the inhibition of GH action. Our findings indicate that the increased expression of FGF21 during chronic undernutrition inhibits GH action on chondrocytes by activating LEPROT and LEPROTL1. 

Retracted: Yes

PubPeer comments:
 Figure 2C. Much more similar than you would expect. https: imgur.com gG0ZKUQ , 
 **Withdrawal: Increased expression of fibroblast growth factor 21 (FGF21) during chronic undernutrition causes growth hormone insensitivity in chondrocytes by inducing leptin receptor overlapping transcript (LEPROT) and leptin receptor overlapping transcript-like 1 (LEPROTL1) expression.** VOLUME 288 (2013) PAGES 27375u201327383 This article has been withdrawn by Shufang Wu, Alexei Kharitonenkov, Julie Dam, Ralf Jockers, and Francesco De Luca. Tal Grunwald could not be reached. In Fig. 1C, lanes 1 and 2 of the actin immunoblot are the same as lanes 3 and 4. In Fig. 2C, lanes 1 and 4 of the LEPROT immunoblot are the same, and lanes 1 and 3 of the LEPROTL1 immunoblot are the same. There is also a splice in the LEPROTL1 immunoblot. The withdrawing authors affirm that all the experimental results and conclusions reported in this manuscript accurately reflect the experimental work carried out in their laboratory. However, given the issues listed above, the withdrawing authors wish to withdraw this article to preserve the full accuracy of the published scientific literature. u00a9 2020 by The American Society for Biochemistry and Molecular Biology, Inc. , 
 https: retractionwatch.com 2020 09 30 author-says-misguided-efforts-for-the-ideal-western-blot-led-to-the-withdrawal-of-these-studies , 
 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 1:  Shufang Wu, Tal Grunwald, Alexei Kharitonenkov, Julie Dam, Ralf Jockers, Francesco De Luca*. **Increased Expression of Fibroblast Growth Factor 21 (FGF21) During Chronic Undernutrition Causes Growth Hormone Insensitivity in Chondrocytes by Inducing Leptin Receptor Overlapping Transcript ( LEPROT) and Leptin Receptor Overlapping Transcript-Like 1 (LEPROTL1) Expression**. J Biol Chem, 2013, 288(38):27375- 27383.u201d (with reference to fund numbers 81071440, 81222026) ... 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 ,