Chen Luen-Kui, Chen Chien-Wei, Wu Shao-Yun, Liu Shui-Yu, Wu Liang-Yi, Chang Chi-Jen, Sy Leticia B, Juan Chi-Chang
Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Department of Physical Education, Health, and Recreation, Teachers College, National Chiayi University, Chiayi 621302, Taiwan.
Int J Med Sci. 2025 Jul 28;22(14):3490-3500. doi: 10.7150/ijms.115524. eCollection 2025.
Obesity is associated with low-grade chronic inflammation, and research has shown that RANTES and CCR5 mRNA levels are notably higher in the visceral adipose tissue of obese individuals compared to lean controls. However, the precise role of CCR5 activation in obesity development is still unclear. This study aims to explore the impact of CCR5 activation on adipogenesis and the underlying regulatory mechanisms. The study used 3T3-F442A preadipocytes and primary preadipocytes from wild-type (WT) and CCR5 knockout (CCR5) mice to assess the role of CCR5 activation in adipocyte differentiation. To investigate the effects of CCR5 on obesity, male C57BL/6J WT and CCR5 mice were fed either a normal chow (NC) or a high-fat diet (HFD) for two months. Plasma RANTES levels, fat pad weight, adipocyte size, and adipose CCR5 expression were measured. Treatment with RANTES resulted in increased intracellular triglyceride accumulation and enhanced expression of adipogenic transcription factors such as PPARγ, C/EBPα, and the adipocyte-specific protein aP2 during differentiation. These findings suggest that RANTES facilitates adipocyte differentiation. Moreover, pretreatment with the CCR5 inhibitor maraviroc and the ERK inhibitor PD98059 significantly reduced RANTES-induced adipocyte differentiation. RANTES also promoted differentiation in primary preadipocytes from WT mice, but not from CCR5 mice. , WT mice on a high-fat diet showed higher plasma RANTES levels and increased adipose CCR5 expression, as well as obesity, whereas these changes were absent in CCR5 mice. The results suggest that CCR5 activation by RANTES enhances adipocyte differentiation via an ERK-dependent pathway, and that CCR5 plays a critical role in the development of obesity.
肥胖与低度慢性炎症相关，研究表明，与瘦对照组相比，肥胖个体内脏脂肪组织中的调节激活正常T细胞表达和分泌因子（RANTES）和C-C趋化因子受体5（CCR5）信使核糖核酸（mRNA）水平显著更高。然而，CCR5激活在肥胖发展中的精确作用仍不清楚。本研究旨在探讨CCR5激活对脂肪生成的影响及其潜在调控机制。该研究使用3T3-F442A前脂肪细胞以及来自野生型（WT）和CCR5基因敲除（CCR5-/-）小鼠的原代前脂肪细胞，以评估CCR5激活在脂肪细胞分化中的作用。为了研究CCR5对肥胖的影响，雄性C57BL/6J WT和CCR5-/-小鼠被喂食正常饲料（NC）或高脂饮食（HFD）两个月。测量血浆RANTES水平、脂肪垫重量、脂肪细胞大小和脂肪组织CCR5表达。在分化过程中，用RANTES处理导致细胞内甘油三酯积累增加，以及脂肪生成转录因子如过氧化物酶体增殖物激活受体γ（PPARγ）、CCAAT增强子结合蛋白α（C/EBPα）和脂肪细胞特异性蛋白aP2的表达增强。这些发现表明RANTES促进脂肪细胞分化。此外，用CCR5抑制剂马拉维若和细胞外信号调节激酶（ERK）抑制剂PD98059预处理显著降低了RANTES诱导的脂肪细胞分化。RANTES也促进了WT小鼠原代前脂肪细胞的分化，但对CCR5-/-小鼠的原代前脂肪细胞没有作用。此外，高脂饮食的WT小鼠血浆RANTES水平更高，脂肪组织CCR5表达增加，同时出现肥胖，而CCR5-/-小鼠没有这些变化。结果表明，RANTES激活CCR5通过ERK依赖途径增强脂肪细胞分化，并且CCR5在肥胖发展中起关键作用。
