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Inhibition of the RPS6KA1/FoxO1 signaling axis by hydroxycitric acid attenuates HFD-induced obesity through MCE suppression.

التفاصيل البيبلوغرافية
العنوان: Inhibition of the RPS6KA1/FoxO1 signaling axis by hydroxycitric acid attenuates HFD-induced obesity through MCE suppression.
المؤلفون: Lee HW; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Woosuk University, Wanju 55338, Republic of Korea., Karki R; Department of Biological Sciences, College of Natural Science, Seoul National University, Seoul 08826, South Korea; Nexus Institute of Research and Innovation (NIRI), Kathmandu, Nepal., Han JH; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Woosuk University, Wanju 55338, Republic of Korea. Electronic address: hanjh5621@woosuk.ac.kr.
المصدر: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Jun; Vol. 128, pp. 155551. Date of Electronic Publication: 2024 Mar 20.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Urban & Fischer Verlag Country of Publication: Germany NLM ID: 9438794 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1618-095X (Electronic) Linking ISSN: 09447113 NLM ISO Abbreviation: Phytomedicine Subsets: MEDLINE
أسماء مطبوعة: Publication: Stuttgart : Urban & Fischer Verlag
Original Publication: Stuttgart ; New York : G. Fischer, c1994-
مواضيع طبية MeSH: Cell Proliferation*/drug effects , Citrates*/pharmacology , Citrates*/therapeutic use , Forkhead Box Protein O1*/antagonists & inhibitors , Forkhead Box Protein O1*/metabolism , Obesity*/drug therapy , Obesity*/metabolism , Ribosomal Protein S6 Kinases, 90-kDa*/antagonists & inhibitors , Ribosomal Protein S6 Kinases, 90-kDa*/metabolism, Animals ; Mice ; 3T3-L1 Cells/drug effects ; Adipocytes/drug effects ; Adipocytes/metabolism ; Adipogenesis/drug effects ; Adipose Tissue, White/drug effects ; Adipose Tissue, White/metabolism ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Mitosis/drug effects ; Signal Transduction/drug effects
مستخلص: Background: Because obesity is associated with a hyperplasia-mediated increase in adipose tissue, inhibiting cell proliferation during mitotic clonal expansion (MCE) is a leading strategy for preventing obesity. Although (-)-hydroxycitric acid (HCA) is used to control obesity, the molecular mechanisms underlying its effects on MCE are poorly understood.
Purpose: This study aimed to investigate the potential effects of HCA on MCE and underlying molecular mechanisms affecting adipogenesis and obesity improvements.
Methods: Preadipocyte cell line, 3T3-L1, were treated with HCA; oil red O, cell proliferation, cell cycle, and related alterations in signaling pathways were examined. High-fat diet (HFD)-fed mice were administered HCA for 12 weeks; body and adipose tissues weights were evaluated, and the regulation of signaling pathways in epidydimal white adipose tissue were examined in vivo.
Results: Here, we report that during MCE, HCA attenuates the proliferation of the preadipocyte cell line, 3T3-L1, by arresting the cell cycle at the G 0 /G 1 phase. In addition, HCA markedly inhibits Forkhead Box O1 (FoxO1) phosphorylation, thereby inducing the expression of cyclin-dependent kinase inhibitor 1B and suppressing the levels of cyclin-dependent kinase 2, cyclin E1, proliferating cell nuclear antigen, and phosphorylated retinoblastoma. Importantly, we found that ribosomal protein S6 kinase A1 (RPS6KA1) influences HCA-mediated inactivation of FoxO1 and its nuclear exclusion. An animal model of obesity revealed that HCA reduced high-fat diet-induced obesity by suppressing adipocyte numbers as well as epididymal and mesenteric white adipose tissue mass, which is attributed to the regulation of RPS6KA1, FoxO1, CDKN1B and PCNA that had been consistently identified in vitro.
Conclusions: These findings provide novel insights into the mechanism by which HCA regulates adipogenesis and highlight the RPS6KA1/FoxO1 signaling axis as a therapeutic target for obesity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All data were generated in-house, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy
(Copyright © 2024 Elsevier GmbH. All rights reserved.)
فهرسة مساهمة: Keywords: Adipogenesis; FoxO1; Hydroxycitric acid; Mitotic clonal expansion; Obesity; RPS6KA1
المشرفين على المادة: 0 (Citrates)
0 (Forkhead Box Protein O1)
0 (Foxo1 protein, mouse)
8W94T9026R (hydroxycitric acid)
EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa)
EC 2.7.11.1 (Rps6ka1 protein, mouse)
تواريخ الأحداث: Date Created: 20240403 Date Completed: 20240430 Latest Revision: 20240510
رمز التحديث: 20240511
DOI: 10.1016/j.phymed.2024.155551
PMID: 38569293
قاعدة البيانات: MEDLINE
الوصف
تدمد:1618-095X
DOI:10.1016/j.phymed.2024.155551