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目的 寻找肥胖能量平衡控制过程中，调控蛋白质翻译启动的关键因子。 方法 通过高通量RNA测序分析肥胖者和健康对照者大网膜脂肪组织中差异表达的mRNA。通过基因本体（gene ontology， GO）富集、京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes， KEGG）通路分析将差异表达的mRNA进行功能富集，围绕真核生物翻译起始家族（eukaryotic translation initiation family，eIFs）进一步分析，并通过GEPIA/GEO数据库验证、免疫印迹实验及qPCR验证eIFs在ob/ob小鼠、db/db小鼠、原代脂肪细胞和C3H10T1/2细胞分化模型中的表达情况。 结果 肥胖症患者大网膜脂肪组织中，翻译起始因子3e（eukaryotic initiation factor 3e， eIF3e）表达量下降显著。 eIF3e与肥胖相关代谢表型和脂肪生成相关基因呈负相关。在培养的原代脂肪细胞和C3H10T1/2细胞诱导分化过程中，发现 eIF3e在脂肪生成过程中发挥负调控作用。在β3肾上腺素能刺激下，在适应性产热小鼠模型和C3H10T1/2细胞中检测到伴随能量的消耗 eIF3e正向升高。 结论 eIF3e在脂肪生成过程中表达下调，且脂肪分解过程中表达上调，提示 eIF3e可能是肥胖能量平衡控制过程中，调控蛋白质翻译启动的关键因子。
","endNoteUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=EndNote&id=755","reference":"| 1 | Laine C， Wee CC. Overweight and obesity： current clinical challenges［J］. Ann Intern Med， 2023， 176（5）： 699. |
| 2 | Ghaben AL， Scherer PE. Adipogenesis and metabolic health［J］. Nat Rev Mol Cell Biol， 2019， 20（4）： 242. |
| 3 | Vishvanath L， Gupta RK. Contribution of adipogenesis to healthy adipose tissue expansion in obesity［J］. J Clin Invest， 2019， 129（10）： 4022. |
| 4 | Harms M， Seale P. Brown and beige fat： development， function and therapeutic potential［J］. Nat Med， 2013， 19（10）： 1252. |
| 5 | Shamsi F， Wang CH， Tseng YH. The evolving view of thermogenic adipocytes - ontogeny， niche and function［J］. Nat Rev Endocrinol， 2021， 17（12）： 726. |
| 6 | Kong J， Lasko P. Translational control in cellular and developmental processes［J］. Nat Rev Genet， 2012， 13（6）： 383. |
| 7 | Wilcox G. Insulin and insulin resistance［J］. Clin Biochem Rev， 2005， 26（2）： 19. |
| 8 | Jackson RJ， Hellen CUT， Pestova TV. The mechanism of eukaryotic translation initiation and principles of its regulation［J］. Nat Rev Mol Cell Biol， 2010， 11（2）： 113. |
| 9 | Levy T， Voeltzke K， Hruby L， et al. mTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism［J］. Nat Commun， 2024， 15（1）： 4083. |
| 10 | Zhou J， Pang J， Tripathi M， et al. Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression［J］. Nat Commun， 2022， 13（1）： 5202. |
| 11 | Scagliola A， Miluzio A， Ventura G， et al. Targeting of eIF6-driven translation induces a metabolic rewiring that reduces NAFLD and the consequent evolution to hepatocellular carcinoma［J］. Nat Commun， 2021， 12（1）： 4878. |
| 12 | Brina D， Miluzio A， Ricciardi S， et al. eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription［J］. Nat Commun， 2015， 6： 8261. |
| 13 | Jo S， Lockridge A， Mohan R， et al. Translational factor eIF4G1 regulates glucose homeostasis and pancreatic β-cell function［J］. Diabetes， 2021， 70（1）： 155. |
| 14 | Lee ASY， Kranzusch PJ， Cate JHD. eIF3 targets cell-proliferation messenger RNAs for translational activation or repression［J］. Nature， 2015， 522（7554）： 111. |
| 15 | Choudhuri A， Maitra U， Evans T. Translation initiation factor eIF3h targets specific transcripts to polysomes during embryogenesis［J］. Proc Natl Acad Sci U S A， 2013， 110（24）： 9818. |
| 16 | Zhou CS， Arslan F， Wee S， et al. PCI proteins eIF3e and eIF3m define distinct translation initiation factor 3 complexes［J］. BMC Biol， 2005， 3： 14. |
| 17 | Miyazaki S， Imatani A， Ballard L， et al. The chromosome location of the human homolog of the mouse mammary tumor-associated gene INT6 and its status in human breast carcinomas［J］. Genomics， 1997， 46（1）： 155. |
| 18 | Grzmil M， Rzymski T， Milani M， et al. An oncogenic role of eIF3e/INT6 in human breast cancer［J］. Oncogene， 2010， 29（28）： 4080. |
| 19 | Li YQ， Zhang DT， Gao YN， et al. METTL3 exacerbates insulin resistance in hepatocytes by regulating m6A modification of cytochrome P450 2B6［J］. Nutr Metab， 2023， 20（1）： 40. |
| 20 | Gross B， Pawlak M， Lefebvre P， et al. PPARs in obesity-induced T2DM， dyslipidaemia and NAFLD［J］. Nat Rev Endocrinol， 2017， 13（1）： 36. |
| 21 | Safaei M， Sundararajan EA， Driss M， et al. A systematic literature review on obesity： understanding the causes & consequences of obesity and reviewing various machine learning approaches used to predict obesity［J］. Comput Biol Med， 2021， 136： 104754. |
| 22 | Blüher M. Adipose tissue inflammation： a cause or consequence of obesity-related insulin resistance？［J］. Clin Sci （Lond）， 2016， 130（18）： 1603. |
| 23 | Fox CS， Massaro JM， Hoffmann U， et al. Abdominal visceral and subcutaneous adipose tissue compartments： association with metabolic risk factors in the Framingham heart study［J］. Circulation， 2007， 116（1）： 39. |
| 24 | Asano K， Merrick WC， Hershey JW. The translation initiation factor eIF3-p48 subunit is encoded byint-6， a site of frequent integration by the mouse mammary tumor virus genome［J］. J Biol Chem， 1997， 272（38）： 23477. |
| 25 | Chong PSY， Chooi JY， Lim SLJ， et al. Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E （eIF3E） by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t（4；14） myeloma［J］. Haematologica， 2024， 109（6）： 1983. |
| 26 | Morris C， Durand S， Jalinot P. Decreased expression of the translation factor eIF3e induces senescence in breast cancer cells via suppression of PARP1 and activation of mTORC1［J］. Oncotarget， 2021， 12（7）： 649. |
| 27 | Sesen J， Cammas A， Scotland SJ， et al. Int6/eIF3e is essential for proliferation and survival of human glioblastoma cells［J］. Int J Mol Sci， 2014， 15（2）： 2172. |
| 28 | Conn CS， Yang HJ， Tom HJ， et al. The major cap-binding protein eIF4E regulates lipid homeostasis and diet-induced obesity［J］. Nat Metab， 2021， 3（2）： 244. |
| 29 | Wang XW， Sun YJ， Chen X， et al. Interleukin-4-induced FABP4 promotes lipogenesis in human skeletal muscle cells by activating the PPAR γ signaling pathway［J］. Cell Biochem Biophys， 2022， 80（2）： 355. |
| 30 | Hertzel AV， Xu HL， Downey M， et al. Fatty acid binding protein 4/aP2-dependent BLT1R expression and signaling［J］. J Lipid Res， 2017， 58（7）： 1354. |
| 31 | Yoon H， Shaw JL， Haigis MC， et al. Lipid metabolism in sickness and in health： emerging regulators of lipotoxicity［J］. Mol Cell， 2021， 81（18）： 3708. |
)","risUrl_cn":"//www.pitakata.com/xuebao/CN/article/getTxtFile.do?fileType=Ris&id=755","title_cn":"eIF3e在肥胖症患者大网膜脂肪组织中的表达及意义","doi":"10.3969/j.issn.2097-0005.2025.02.002","jieShuYe":"82","keywordList_en":["obesity","omental adipose tissue","eukaryotic translation initiation factors","eIF3e","translational control"],"endNoteUrl_cn":"//www.pitakata.com/xuebao/CN/article/getTxtFile.do?fileType=EndNote&id=755","zhaiyao_en":"Objective Find the key factors regulating the initiation of protein translation in the process of controlling energy balance in obesity. Methods This study analyzes the differentially expressed mRNAs in omental adipose tissue of obese individuals and healthy controls by high-throughput RNA sequencing， and finds abnormal translation initiation levels. The differentially expressed mRNAs are functionally enriched by GO enrichment and KEGG pathway analysis， and further analyzed around the eukaryotic translation initiation family （eukaryotic translation initiation family， eIFs）， and the expression of eIFs in ob/ob mice， db/db mice， primary adipocytes and C3H10T1/2 cell differentiation models is verified by GEPIA/GEO database verification， Western blotting experiments and qPCR. Results In the omental adipose tissue of obese patients， the expression of translation initiation factor 3e （eIF3e） decreases significantly. The GEPIA/GEO database confirms the negative correlation between eIF3e and obesity-related metabolic phenotypes and adipogenesis-related genes. During the induction and differentiation of primary adipocytes and C3H10T1/2 cells in culture， the negative regulatory role of eIF3e in adipogenesis has been discovered. Under β3 adrenergic stimulation， the positive increase of eIF3e accompanied by energy expenditure has been detected in the adaptive thermogenesis mouse model and C3H10T1/2 cells. Conclusion eIF3e is downregulated during adipogenesis and upregulated during lipolysis， suggesting that eIF3e may be a key factor in regulating the initiation of protein translation during the control of energy balance in obesity.
","bibtexUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=BibTeX&id=755","abstractUrl_cn":"http://xuebao.sdfmu.edu.cn/CN/10.3969/j.issn.2097-0005.2025.02.002","zuoZheCn_L":"马筱璇, 高菲, 逯素梅, 玄晓蕾, 张永娇, 石晓红","juanUrl_cn":"http://xuebao.sdfmu.edu.cn/CN/Y2025","lanMu_en":"Basic Researches","qiUrl_en":"//www.pitakata.com/xuebao/EN/Y2025/V46/I2","zuoZhe_EN":"Xiaoxuan MA1, Fei GAO1, Sumei LU1, Xiaolei XUAN1, Yongjiao ZHANG1,2, Xiaohong SHI1()","risUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=Ris&id=755","title_en":"Expression and significance of eIF3e in the adipose tissue of the greater omentum in patients with obesity","hasPdf":"true"},"authorNotes_cn":["石晓红，E-mail：S20739@163.com。
Expression and significance of eIF3e in the adipose tissue of the greater omentum in patients with obesity
Xiaoxuan MA, Fei GAO, Sumei LU, Xiaolei XUAN, Yongjiao ZHANG, Xiaohong SHI
Journal of ShanDong First Medical University&ShanDong Academy of Medical Sciences››2025, Vol. 46››Issue (2): 72-82.
PDF(6551 KB)
PDF(6551 KB)
Expression and significance of eIF3e in the adipose tissue of the greater omentum in patients with obesity
ObjectiveFind the key factors regulating the initiation of protein translation in the process of controlling energy balance in obesity.MethodsThis study analyzes the differentially expressed mRNAs in omental adipose tissue of obese individuals and healthy controls by high-throughput RNA sequencing， and finds abnormal translation initiation levels. The differentially expressed mRNAs are functionally enriched by GO enrichment and KEGG pathway analysis， and further analyzed around the eukaryotic translation initiation family （eukaryotic translation initiation family， eIFs）， and the expression of eIFs in ob/ob mice， db/db mice， primary adipocytes and C3H10T1/2 cell differentiation models is verified by GEPIA/GEO database verification， Western blotting experiments and qPCR.ResultsIn the omental adipose tissue of obese patients， the expression of translation initiation factor 3e （eIF3e） decreases significantly. The GEPIA/GEO database confirms the negative correlation between eIF3e and obesity-related metabolic phenotypes and adipogenesis-related genes. During the induction and differentiation of primary adipocytes and C3H10T1/2 cells in culture， the negative regulatory role of eIF3e in adipogenesis has been discovered. Under β3 adrenergic stimulation， the positive increase of eIF3e accompanied by energy expenditure has been detected in the adaptive thermogenesis mouse model and C3H10T1/2 cells.ConclusioneIF3e is downregulated during adipogenesis and upregulated during lipolysis， suggesting that eIF3e may be a key factor in regulating the initiation of protein translation during the control of energy balance in obesity.
obesity/omental adipose tissue/eukaryotic translation initiation factors/eIF3e/translational control
| 1 | Laine C， Wee CC. Overweight and obesity： current clinical challenges［J］.Ann Intern Med，2023，176（5）： 699. |
| 2 | Ghaben AL， Scherer PE. Adipogenesis and metabolic health［J］.Nat Rev Mol Cell Biol，2019，20（4）： 242. |
| 3 | Vishvanath L， Gupta RK. Contribution of adipogenesis to healthy adipose tissue expansion in obesity［J］.J Clin Invest，2019，129（10）： 4022. |
| 4 | Harms M， Seale P. Brown and beige fat： development， function and therapeutic potential［J］.Nat Med，2013，19（10）： 1252. |
| 5 | Shamsi F， Wang CH， Tseng YH. The evolving view of thermogenic adipocytes - ontogeny， niche and function［J］.Nat Rev Endocrinol，2021，17（12）： 726. |
| 6 | Kong J， Lasko P. Translational control in cellular and developmental processes［J］.Nat Rev Genet，2012，13（6）： 383. |
| 7 | Wilcox G. Insulin and insulin resistance［J］.Clin Biochem Rev，2005，26（2）： 19. |
| 8 | Jackson RJ， Hellen CUT， Pestova TV. The mechanism of eukaryotic translation initiation and principles of its regulation［J］.Nat Rev Mol Cell Biol，2010，11（2）： 113. |
| 9 | Levy T， Voeltzke K， Hruby L， et al. mTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism［J］.Nat Commun，2024，15（1）： 4083. |
| 10 | Zhou J， Pang J， Tripathi M， et al. Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression［J］.Nat Commun，2022，13（1）： 5202. |
| 11 | Scagliola A， Miluzio A， Ventura G， et al. Targeting of eIF6-driven translation induces a metabolic rewiring that reduces NAFLD and the consequent evolution to hepatocellular carcinoma［J］.Nat Commun，2021，12（1）： 4878. |
| 12 | Brina D， Miluzio A， Ricciardi S， et al. eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription［J］.Nat Commun，2015，6： 8261. |
| 13 | Jo S， Lockridge A， Mohan R， et al. Translational factor eIF4G1 regulates glucose homeostasis and pancreatic β-cell function［J］.Diabetes，2021，70（1）： 155. |
| 14 | Lee ASY， Kranzusch PJ， Cate JHD. eIF3 targets cell-proliferation messenger RNAs for translational activation or repression［J］.Nature，2015，522（7554）： 111. |
| 15 | Choudhuri A， Maitra U， Evans T. Translation initiation factor eIF3h targets specific transcripts to polysomes during embryogenesis［J］.Proc Natl Acad Sci U S A，2013，110（24）： 9818. |
| 16 | Zhou CS， Arslan F， Wee S， et al. PCI proteins eIF3e and eIF3m define distinct translation initiation factor 3 complexes［J］.BMC Biol，2005，3： 14. |
| 17 | Miyazaki S， Imatani A， Ballard L， et al. The chromosome location of the human homolog of the mouse mammary tumor-associated gene INT6 and its status in human breast carcinomas［J］.Genomics，1997，46（1）： 155. |
| 18 | Grzmil M， Rzymski T， Milani M， et al. An oncogenic role of eIF3e/INT6 in human breast cancer［J］.Oncogene，2010，29（28）： 4080. |
| 19 | Li YQ， Zhang DT， Gao YN， et al. METTL3 exacerbates insulin resistance in hepatocytes by regulating m6A modification of cytochrome P450 2B6［J］.Nutr Metab，2023，20（1）： 40. |
| 20 | Gross B， Pawlak M， Lefebvre P， et al. PPARs in obesity-induced T2DM， dyslipidaemia and NAFLD［J］.Nat Rev Endocrinol，2017，13（1）： 36. |
| 21 | Safaei M， Sundararajan EA， Driss M， et al. A systematic literature review on obesity： understanding the causes & consequences of obesity and reviewing various machine learning approaches used to predict obesity［J］.Comput Biol Med，2021，136： 104754. |
| 22 | Blüher M. Adipose tissue inflammation： a cause or consequence of obesity-related insulin resistance？［J］.Clin Sci （Lond），2016，130（18）： 1603. |
| 23 | Fox CS， Massaro JM， Hoffmann U， et al. Abdominal visceral and subcutaneous adipose tissue compartments： association with metabolic risk factors in the Framingham heart study［J］.Circulation，2007，116（1）： 39. |
| 24 | Asano K， Merrick WC， Hershey JW. The translation initiation factor eIF3-p48 subunit is encoded byint-6， a site of frequent integration by the mouse mammary tumor virus genome［J］.J Biol Chem，1997，272（38）： 23477. |
| 25 | Chong PSY， Chooi JY， Lim SLJ， et al. Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E （eIF3E） by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t（4；14） myeloma［J］.Haematologica，2024，109（6）： 1983. |
| 26 | Morris C， Durand S， Jalinot P. Decreased expression of the translation factor eIF3e induces senescence in breast cancer cells via suppression of PARP1 and activation of mTORC1［J］.Oncotarget，2021，12（7）： 649. |
| 27 | Sesen J， Cammas A， Scotland SJ， et al. Int6/eIF3e is essential for proliferation and survival of human glioblastoma cells［J］.Int J Mol Sci，2014，15（2）： 2172. |
| 28 | Conn CS， Yang HJ， Tom HJ， et al. The major cap-binding protein eIF4E regulates lipid homeostasis and diet-induced obesity［J］.Nat Metab，2021，3（2）： 244. |
| 29 | Wang XW， Sun YJ， Chen X， et al. Interleukin-4-induced FABP4 promotes lipogenesis in human skeletal muscle cells by activating the PPAR γ signaling pathway［J］.Cell Biochem Biophys，2022，80（2）： 355. |
| 30 | Hertzel AV， Xu HL， Downey M， et al. Fatty acid binding protein 4/aP2-dependent BLT1R expression and signaling［J］.J Lipid Res，2017，58（7）： 1354. |
| 31 | Yoon H， Shaw JL， Haigis MC， et al. Lipid metabolism in sickness and in health： emerging regulators of lipotoxicity［J］.Mol Cell，2021，81（18）： 3708. |
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