RNA binding protein HuD regulates fatty acid oxidation in pancreatic β-cells by modulating long-chain acyl-CoA dehydrogenase expression

RNA binding proteins (RBPs) play crucial roles in the post-transcriptional regulation of metabolic pathways. Although the RBP HuD has been extensively studied in pancreatic β-cells, its role in cellular metabolism remains poorly understood. In this study, we uncover a novel function of HuD in regula...

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Main Authors: Jiyoon Seo, Seungyeon Ryu, Wei Zhang, Eun Kyung Lee, Seung Min Jeong
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Animal Cells and Systems
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Online Access:https://www.tandfonline.com/doi/10.1080/19768354.2025.2542168
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author Jiyoon Seo
Seungyeon Ryu
Wei Zhang
Eun Kyung Lee
Seung Min Jeong
author_facet Jiyoon Seo
Seungyeon Ryu
Wei Zhang
Eun Kyung Lee
Seung Min Jeong
author_sort Jiyoon Seo
collection DOAJ
description RNA binding proteins (RBPs) play crucial roles in the post-transcriptional regulation of metabolic pathways. Although the RBP HuD has been extensively studied in pancreatic β-cells, its role in cellular metabolism remains poorly understood. In this study, we uncover a novel function of HuD in regulating fatty acid oxidation (FAO) in mouse insulinoma βTC6 cells. Through genetic knockdown and overexpression approaches, we demonstrate that HuD modulates the expression of long-chain acyl-CoA dehydrogenase (LCAD), a key enzyme in FAO, by binding to the 3′-untranslated region of its mRNA. Loss of HuD impaired FAO, leading to lipid droplet accumulation, elevated reactive oxygen species production, and increased lipotoxicity under lipid-stress conditions. These findings reveal a previously unrecognized role for HuD in maintaining fatty acid homeostasis and suggest that the HuD-LCAD regulatory axis may represent a promising therapeutic target for preserving β-cell integrity and function.
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institution Kabale University
issn 1976-8354
2151-2485
language English
publishDate 2025-12-01
publisher Taylor & Francis Group
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series Animal Cells and Systems
spelling doaj-art-0fac34e0e15f4a93b0f13c7cd0887fd92025-08-20T03:40:41ZengTaylor & Francis GroupAnimal Cells and Systems1976-83542151-24852025-12-0129151252210.1080/19768354.2025.2542168RNA binding protein HuD regulates fatty acid oxidation in pancreatic β-cells by modulating long-chain acyl-CoA dehydrogenase expressionJiyoon Seo0Seungyeon Ryu1Wei Zhang2Eun Kyung Lee3Seung Min Jeong4Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaShanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaRNA binding proteins (RBPs) play crucial roles in the post-transcriptional regulation of metabolic pathways. Although the RBP HuD has been extensively studied in pancreatic β-cells, its role in cellular metabolism remains poorly understood. In this study, we uncover a novel function of HuD in regulating fatty acid oxidation (FAO) in mouse insulinoma βTC6 cells. Through genetic knockdown and overexpression approaches, we demonstrate that HuD modulates the expression of long-chain acyl-CoA dehydrogenase (LCAD), a key enzyme in FAO, by binding to the 3′-untranslated region of its mRNA. Loss of HuD impaired FAO, leading to lipid droplet accumulation, elevated reactive oxygen species production, and increased lipotoxicity under lipid-stress conditions. These findings reveal a previously unrecognized role for HuD in maintaining fatty acid homeostasis and suggest that the HuD-LCAD regulatory axis may represent a promising therapeutic target for preserving β-cell integrity and function.https://www.tandfonline.com/doi/10.1080/19768354.2025.2542168HuDLCADfatty acid oxidationlipotoxicitypancreatic β-cell
spellingShingle Jiyoon Seo
Seungyeon Ryu
Wei Zhang
Eun Kyung Lee
Seung Min Jeong
RNA binding protein HuD regulates fatty acid oxidation in pancreatic β-cells by modulating long-chain acyl-CoA dehydrogenase expression
Animal Cells and Systems
HuD
LCAD
fatty acid oxidation
lipotoxicity
pancreatic β-cell
title RNA binding protein HuD regulates fatty acid oxidation in pancreatic β-cells by modulating long-chain acyl-CoA dehydrogenase expression
title_full RNA binding protein HuD regulates fatty acid oxidation in pancreatic β-cells by modulating long-chain acyl-CoA dehydrogenase expression
title_fullStr RNA binding protein HuD regulates fatty acid oxidation in pancreatic β-cells by modulating long-chain acyl-CoA dehydrogenase expression
title_full_unstemmed RNA binding protein HuD regulates fatty acid oxidation in pancreatic β-cells by modulating long-chain acyl-CoA dehydrogenase expression
title_short RNA binding protein HuD regulates fatty acid oxidation in pancreatic β-cells by modulating long-chain acyl-CoA dehydrogenase expression
title_sort rna binding protein hud regulates fatty acid oxidation in pancreatic β cells by modulating long chain acyl coa dehydrogenase expression
topic HuD
LCAD
fatty acid oxidation
lipotoxicity
pancreatic β-cell
url https://www.tandfonline.com/doi/10.1080/19768354.2025.2542168
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