임지희 (가톨릭대학교 의과대학)

한빛사논문

조회149

가톨릭대학교 의과대학

Metab.-Clin. Exp., Aug 20 2024, S0026-0495(24)00229-4 | https://doi.org/10.1016/j.metabol.2024.156002 Placental growth factor deficiency initiates obesity- and aging-associated metabolic syndrome

Ji Hee Lim^a,b, Yaeni Kim ^a, Min Young Kim ^a,b, Eun Nim Kim ^a, Tae Woo Kim ^a, Bum Soon Choi ^a, Wan-Uk Kim ^c, Hye Won Kim ^d, Ji Yong Park ^e, Cheol Whee Park ^a,b

^aDivision of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

^bInstitute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

^cDivision of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

^dDepartment of Rehabilitation Medicine, , Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Republic of Korea

^eDepartment of Psychology, Korea University, Seoul, Republic of Korea

Corresponding author: Cheol Whee Park

Abstract

Obesity often leads to inadequate angiogenesis in expanding adipose tissue, resulting in inflammation and insulin resistance. We explored the role of placental growth factor (PlGF) in metabolic syndrome (MS) using mice models of type 2 diabetes, high-fat diet, or aging. Reduced serum PlGF levels were associated with decreased insulin sensitivity and development of MS features. PlGF was localized within endothelial cells and pericytes of adipose tissue. In vitro, low PlGF levels in hypoxic conditions worsened oxidative stress, apoptosis, and reduced autophagy. This was associated with a reduction in expression of vascular endothelial growth factor (VEGF)-A/VEGF-R1/-R2, which was influenced by a decrease and increase in PlGF/pAMPK/PI3K-pAkt/PLCγ1-iCa⁺⁺/eNOS and PTEN/GSK3β axes, respectively. PlGF-knockout mice exhibited MS traits through alterations in the same signaling pathways, and these changes were mitigated by recombinant PlGF and metformin. These enhanced angiogenesis and lipid metabolism, underscoring PlGF's role in age-related MS and its potential as a therapeutic target.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-08-29)
연구진국내 연구진
분야 의약학 > 응용의학

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