Hoon Jang1, Hyoung-Joo Kim2, Dong-Hwan Kim1, Jae-Kyung Park2, Wu-Sheng Sun2, Seongsoo Hwang3, Keon-Bong Oh3, Won-Gu Jang4, Jeong-Woong Lee5. 1. Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Functional Genomics, School of Engineering, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea. 2. Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea. 3. Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, Republic of Korea. 4. Department of Biotechnology, School of Engineering, Daegu University, Gyeongbuk 712-714, Republic of Korea. Electronic address: jangwg@daegu.ac.kr. 5. Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Functional Genomics, School of Engineering, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea. Electronic address: jwlee@kribb.re.kr.
Abstract
AIMS: Adipocytes play a critical role in energy balance. Growth of fat tissue is achieved via an increase in adipocyte mass and the formation of newly differentiated adipocytes from precursor cells. Understanding the cellular and molecular mechanisms of adipocyte differentiation is crucial for the study of obesity- and fat-related diseases. The present study was designed to study whether small heterodimer partner-interacting leucine zipper protein (SMILE), a novel co-repressor, could regulate differentiation of adipocyte in 3T3-L1 cells. MATERIALS AND METHODS: Treatment of endoplasmic stress inducers, thapsigargin and tunicamycin, inhibited adipocyte differentiation, stimulated Smile mRNA expression, and repressed the expression of adiponectin (Adipoq) in 3T3-L1 pre-adipocyte. Overexpression of SMILE in 3T3-L1 cells decreased the expression of the mRNA encoding Adipoq, a major marker of adipocytes, significantly. Furthermore, knockdown of SMILE recovered the thapsigargin-mediated repression of Adipoq transcription. Co-immunoprecipitation experiments revealed that SMILE interacted physically with PPARγ in 3T3-L1 cells. In addition, chromatin immunoprecipitation experiments revealed that SMILE suppressed the binding affinity of PPARγ for the Adipoq promoter. KEY FINDINGS: We demonstrate that SMILE controls adipocyte differentiation by regulating the transactivity of peroxisome proliferator-activated receptor γ (PPARγ). SIGNIFICANCE: These findings demonstrate that SMILE represses adipocyte differentiation by regulating PPARγ transactivity; hence, SMILE is a potential regulator of PPARγ-related diseases.
AIMS: Adipocytes play a critical role in energy balance. Growth of fat tissue is achieved via an increase in adipocyte mass and the formation of newly differentiated adipocytes from precursor cells. Understanding the cellular and molecular mechanisms of adipocyte differentiation is crucial for the study of obesity- and fat-related diseases. The present study was designed to study whether small heterodimer partner-interacting leucine zipper protein (SMILE), a novel co-repressor, could regulate differentiation of adipocyte in 3T3-L1 cells. MATERIALS AND METHODS: Treatment of endoplasmic stress inducers, thapsigargin and tunicamycin, inhibited adipocyte differentiation, stimulated Smile mRNA expression, and repressed the expression of adiponectin (Adipoq) in 3T3-L1 pre-adipocyte. Overexpression of SMILE in 3T3-L1 cells decreased the expression of the mRNA encoding Adipoq, a major marker of adipocytes, significantly. Furthermore, knockdown of SMILE recovered the thapsigargin-mediated repression of Adipoq transcription. Co-immunoprecipitation experiments revealed that SMILE interacted physically with PPARγ in 3T3-L1 cells. In addition, chromatin immunoprecipitation experiments revealed that SMILE suppressed the binding affinity of PPARγ for the Adipoq promoter. KEY FINDINGS: We demonstrate that SMILE controls adipocyte differentiation by regulating the transactivity of peroxisome proliferator-activated receptor γ (PPARγ). SIGNIFICANCE: These findings demonstrate that SMILE represses adipocyte differentiation by regulating PPARγ transactivity; hence, SMILE is a potential regulator of PPARγ-related diseases.
Authors: Soon Man Yoon; Talin Haritunians; Sultan Chhina; Zhenqiu Liu; Shaohong Yang; Carol Landers; Dalin Li; Byong Duk Ye; David Shih; Eric A Vasiliauskas; Andrew Ippoliti; Shervin Rabizadeh; Stephan R Targan; Gil Y Melmed; Dermot P B McGovern Journal: Inflamm Bowel Dis Date: 2017-08 Impact factor: 5.325