Zhou Rui, Liu Yajing, Hu Weiqian, Yang Jing, Lin Bing, Zhang Zhentian, Chen Mingyan, Yi Jingwen, Zhu Cuifeng
Acta Biochim Biophys Sin (Shanghai). 2024 Jun 25;56(6):844-856. doi: 10.3724/abbs.2024046.
Lipid droplets (LDs) are dynamic organelles that store neutral lipids and are closely linked to obesity. Previous studies have suggested that polysaccharide (LBP) supplements can ameliorate obesity, but the underlying mechanisms remain unclear. In this study, we hypothesize that LBP alleviates LD accumulation in adipose tissue (AT) by inhibiting fat-specific protein 27 (Fsp27) through an activating transcription factor-6 (ATF6)/small-molecule sirtuin 1 (SIRT1)-dependent mechanism. LD accumulation in AT is induced in high-fat diet (HFD)-fed mice, and differentiation of 3T3-L1 preadipocytes (PAs) is induced. The ability of LBP to alleviate LD accumulation and the possible underlying mechanism are then investigated both and . The influences of LBP on the expressions of LD-associated genes ( and ) are also detected. The results show that HFD and PA differentiation markedly increase LD accumulation in ATs and adipocytes, respectively, and these effects are markedly suppressed by LBP supplementation. Furthermore, LBP significantly activates SIRT1 and decreases ATF6 and Fsp27 expressions. Interestingly, the inhibitory effects of LBP are either abolished or exacerbated when is overexpressed or silenced, respectively. Furthermore, SIRT1 level is transcriptionally regulated by LBP through opposite actions mediated by ATF6. Collectively, our findings suggest that LBP supplementation alleviates obesity by ameliorating LD accumulation, which might be partially mediated by an ATF6/SIRT1-dependent mechanism.
脂滴（LDs）是储存中性脂质的动态细胞器，与肥胖密切相关。先前的研究表明，多糖（LBP）补充剂可以改善肥胖，但潜在机制仍不清楚。在本研究中，我们假设LBP通过激活转录因子6（ATF6）/小分子沉默调节蛋白1（SIRT1）依赖性机制抑制脂肪特异性蛋白27（Fsp27），从而减轻脂肪组织（AT）中的脂滴积累。在高脂饮食（HFD）喂养的小鼠中诱导AT中的脂滴积累，并诱导3T3-L1前脂肪细胞（PAs）分化。然后在体内和体外研究LBP减轻脂滴积累的能力及其可能的潜在机制。还检测了LBP对脂滴相关基因（和）表达的影响。结果表明，HFD和PA分化分别显著增加了AT和脂肪细胞中的脂滴积累，而LBP补充剂可显著抑制这些作用。此外，LBP显著激活SIRT1并降低ATF6和Fsp27的表达。有趣的是，当分别过表达或沉默时，LBP的抑制作用要么被消除，要么被增强。此外，LBP通过ATF6介导的相反作用对SIRT1水平进行转录调控。总的来说，我们的研究结果表明，补充LBP可通过改善脂滴积累来减轻肥胖，这可能部分由ATF6/SIRT1依赖性机制介导。
