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Abstract：
Lipid droplets (LDs) are dynamic organelles that store neutral lipids and are closely linked to obesity. Previous studies have suggested that Lycium barbarum 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 in vivo and in vitro. The influences of LBP on the expressions of LD-associated genes ( ATF6 and Fsp27) 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 ATF6 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.
摘要：
脂滴（LD）是储存中性脂质的动态细胞器，与肥胖密切相关。以前的研究表明，枸杞多糖（LBP）补充剂可以改善肥胖，但潜在的机制仍不清楚。在这项研究中,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LD的积累.在高脂饮食（HFD）喂养的小鼠中诱导了AT中的LD积累，并诱导3T3-L1前脂肪细胞（PAs）的分化。然后在体内和体外研究了LBP减轻LD积累的能力以及可能的潜在机制。还检测了LBP对LD相关基因（ATF6和Fsp27）表达的影响。结果表明，HFD和PA分化显著增加AT和脂肪细胞中LD的积累，分别,这些影响被LBP补充显著抑制。此外，LBP显著激活SIRT1并降低ATF6和Fsp27表达。有趣的是,当ATF6过表达或沉默时，LBP的抑制作用被消除或加剧，分别。此外，SIRT1水平通过ATF6介导的相反作用由LBP转录调节。总的来说，我们的研究结果表明，LBP补充剂通过改善LD积累来缓解肥胖，可能部分由ATF6/SIRT1依赖性机制介导。
