박시영 (가천대 길병원 가천의생명융합연구원 / 가천대학교 한국마우스대사표현형연구센터) | 한빛사논문 > 한빛사

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가천대 길병원 가천의생명융합연구원 / 가천대학교 한국마우스대사표현형연구센터

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J. Adv. Res., Apr 09 2025, S2090-1232(25)00229-2 | https://doi.org/10.1016/j.jare.2025.04.010 ARHGEF3 coordinates adipocyte hypertrophy and differentiation through dual YAP-RhoA and PPARγ activation

Sana Abdul Khaliq ^a,b,1, Shi-Young Park ^c,d,1, Syeda Maham ^a, Yoonil Cho ^a,d, Miseon Lee ^e, Seungyoon Nam ^a,e, Je Kyung Seong ^f,g, Jie Chen ^h, Cheol Soo Choi ^b,d,i, Mee-Sup Yoon ^a,b,j

^aDepartment of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences & Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea
^bDepartment of Molecular Medicine, Gachon University College of Medicine, Incheon 21999, Republic of Korea
^cGachon Biomedical Convergence Institute, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea
^dKorea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
^eDepartment of Genome Medicine and Science, Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea
^fLaboratory of Developmental Biology and Genomics, Research Institute for Veterinary Science, and BK21 FOUR Future Veterinary Medicine Leading Education and Research Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea
^gKorea Model Animal Priority Center (KMPC), Seoul National University, Seoul 08826, Republic of Korea
^hDepartment of Cell & Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
ⁱDepartment of Internal Medicine, Gil Medical Center, Gachon University, Incheon 21565, Republic of Korea
^jLee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea

¹These authors equally contributed.
Corresponding authors: Cheol Soo Choi, Mee-Sup Yoon

Abstract

Introduction: Obesity presents a significant global health burden, necessitating insights into the molecular drivers of adipogenesis and adipose tissue regulation.

Objectives: This study investigates the role of Rho guanine nucleotide exchange factor 3 (ARHGEF3) in adipocyte differentiation and hypertrophy, focusing on its influence on adipogenesis and body weight regulation under high-fat diet conditions.

Methods: ARHGEF3-/- mice and littermate controls were subjected to a high-fat diet (HFD) and underwent comprehensive metabolic phenotyping. In vitro studies in C3H10T1/2 cells were conducted to assess ARHGEF3's role in adipogenesis, utilizing quantitative PCR, western blotting, chromatin immunoprecipitation (ChIP), immunoprecipitation (IP), immunostaining, and luciferase reporter assays.

Results: ARHGEF3 expression increased in white adipose tissue (WAT) of HFD-fed mice and during adipogenic differentiation in C3H10T1/2 cells. ARHGEF3-deficient mice exhibited reduced weight gain and adipocyte size, correlating with decreased RhoA expression and altered cytoskeletal dynamics. Additionally, ARHGEF3 facilitated yes-associated protein (YAP) nuclear translocation and its direct binding to the RhoA promoter, an effect reliant on ARHGEF3. ARHGEF3 also enhanced the transcriptional activity of peroxisome proliferator-activated receptor gamma (PPARγ), establishing a reciprocal activation loop to drive adipocyte differentiation and hypertrophy.

Conclusion: ARHGEF3 emerges as a pivotal regulator of adipocyte dynamics by coordinating YAP-RhoA signaling and enhancing PPARγ activity. These findings offer novel therapeutic insights for addressing obesity and related metabolic disorders.

논문정보

형식Research article
게재일2025년 04월 (BRIC 등록일 2025-04-15)
연구진국내(교신)+국외 연구진
분야 의약학 > 분자세포의학

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