Cahyadi Danang Dwi, Warita Katsuhiko, Takeda-Okuda Naoko, Tamura Jun-Ichi, Hosaka Yoshinao Z
Joint Graduate School of Veterinary Sciences, Tottori University, Tottori, 680-8553, Japan.
Division of Anatomy Histology and Embryology, School of Veterinary Medicine and Biomedical Sciences, IPB University, Bogor, 16680, Indonesia.
Glycoconj J. 2025 Apr;42(2):77-86. doi: 10.1007/s10719-025-10183-0. Epub 2025 Mar 10.
In this study, we investigated for cell proliferative and adipogenic differentiation inhibitory activities of chondroitin sulfate (CS) from cartilaginous fish: mako shark (Isurus oxyrinchus, spine part, Ms-CS), blue shark (Prionace glauca, spine part, Bs-CS), sharpspine skate (Okamejei acutispina, head and tail parts, Sp-CS) and stingray (Dasyatis akajei, head part, St-CS) on 3T3-L1 cells. Most of the CSs from cartilaginous fish showed concentration-dependent cell proliferative activity of 3T3-L1 cells within the retrieved concentration range (0-1,000 μg/mL), while under induction of adipocyte differentiation, they inhibited lipid accumulation. In particular, Ms-CS and Sp-CS were highly active in inhibiting lipid accumulation in the cells. The present study revealed that cartilaginous fish-derived CS has inhibitory activity on 3T3-L1 adipocyte differentiation by suppressing lipid droplet accumulation, although the degree of suppression varied depending on the composition of the CS and its origin. In addition, a significant increase in chondroitin sulfate N-acetylgalactosaminyltransferase 2 (Csgalnact2) expression of the Sp-CS group at the concentration of 500 µg/mL was observed. Csgalnact2 expression is associated with chondroitin N-acetylgalactosaminyltransferase-2 (ChGn-2), one of the glycosyltransferases that catalyzes the chain initiation and elongation of the CS backbone in its biosynthesis. Exogenous CS from cartilaginous fishes increased Csgalnact2 expression, although further studies are needed to confirm changes in CS biosynthesis. We observed reduced lipid accumulation in differentiated 3T3-L1 cells. Our findings highlight the role of CS polysaccharides, in inhibiting adipogenesis, even though further investigation is required to understand the underlying mechanism.
在本研究中,我们调查了软骨鱼类硫酸软骨素(CS)对3T3-L1细胞的细胞增殖和脂肪生成分化抑制活性,这些软骨鱼类包括:灰鲭鲨(尖吻鲭鲨,脊柱部分,Ms-CS)、蓝鲨(大青鲨,脊柱部分,Bs-CS)、尖鳍鳐(尖鳍鳐,头和尾部,Sp-CS)和黄貂鱼(赤魟,头部,St-CS)。在检索到的浓度范围(0-1000μg/mL)内,大多数软骨鱼类来源的CS对3T3-L1细胞表现出浓度依赖性的细胞增殖活性,而在脂肪细胞分化诱导下,它们抑制脂质积累。特别是,Ms-CS和Sp-CS在抑制细胞内脂质积累方面具有高活性。本研究表明,软骨鱼类来源的CS通过抑制脂滴积累对3T3-L1脂肪细胞分化具有抑制活性,尽管抑制程度因CS的组成及其来源而异。此外,在500μg/mL浓度下观察到Sp-CS组硫酸软骨素N-乙酰半乳糖胺基转移酶2(Csgalnact2)表达显著增加。Csgalnact2表达与软骨素N-乙酰半乳糖胺基转移酶-2(ChGn-2)相关,ChGn-2是一种糖基转移酶,在其生物合成中催化CS主链的链起始和延伸。来自软骨鱼类的外源性CS增加了Csgalnact2表达,尽管需要进一步研究来证实CS生物合成的变化。我们观察到分化的3T3-L1细胞中脂质积累减少。我们的研究结果突出了CS多糖在抑制脂肪生成中的作用,尽管需要进一步研究来了解其潜在机制。