Astragalus polysaccharide inhibits lipogenesis in HFD-fed mice by suppressing LIPG via upregulation of UDPG

IF 23.2 2区 材料科学 Q1 MATERIALS SCIENCE, COMPOSITES
Xuelin Wang, Mengying Li, Fang Yu, Limin Hou, Rui Cao, Lei Zhang, Jianwu Xie, Feng Wang, Junrong Huang
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引用次数: 0

Abstract

Astragalus polysaccharide (APS) is a natural active material widely used in the biomedical fields, which is applied in the preparation of capsule shells, nano-coated materials, medical hydrogel systems, and emulsifiers. It has been reported that APS exhibits a beneficial effect on obesity although the molecular mechanisms are not clearly elucidated. In current study, APS significantly reduced the increase of body weight in high-fat diet (HFD) fed mice. APS apparently ameliorated serum lipid profiles exhibiting an increase of high-density lipoprotein and a decrease of low-density lipoprotein. APS inhibited lipid deposition in liver and adipose tissues. Importantly, APS did not damage liver and kidney function in vivo. To explore if the beneficial effect of APS on obesity was derived from its effect on metabolism, metabolomics was applied. As expected, the metabolite profile of HFD mice was dramatically altered upon APS treatment. Among them, uridine diphosphate glucose (UDPG), a glycometabolic intermediate that inhibits fatty acid production, was significantly upregulated by APS. KEGG analysis showed that the metabolites of APS-treated HFD mice were apparently enriched in biosynthesis of unsaturated fatty acids pathway. To further explore if APS altered metabolites impacted cellular biological functions, transcriptomics was performed. GO and KEGG analysis showed that the downregulated gene groups were mainly enriched in lipid metabolism. Furthermore, endothelial lipase (LIPG) responsible for the intracellular lipid production was among the significantly inhibited genes by APS. Above results highly hinted that inhibition of lipid deposition by APS may be closely related with UDPG and LIPG. As expected, LIPG level was greatly suppressed by APS in free fatty acid (FFA)-induced hepatocytes. Consistently, glycogen synthesis was increased, whereas lipogenesis was apparently suppressed by APS. Furthermore, UDPG treatment alone also inhibited LIPG expression and lipogenesis. We, for the first time, disclosed that APS inhibited lipogenesis in HFD-fed mice by suppressing LIPG via upregulation of UDPG, suggesting that APS may be explored as a clinical and translational candidate in preventing obesity and its related metabolic diseases.

黄芪多糖通过上调 UDPG 抑制 LIPG,从而抑制高密度脂蛋白胆固醇(HFD)喂养小鼠的脂肪生成
黄芪多糖(APS)是一种天然活性材料,广泛应用于生物医学领域,可用于制备胶囊壳、纳米涂层材料、医用水凝胶系统和乳化剂。据报道,APS 对肥胖症有一定的疗效,但其分子机制尚未明确阐明。在目前的研究中,APS 明显降低了高脂饮食(HFD)喂养小鼠体重的增加。APS 明显改善了血清脂质状况,表现出高密度脂蛋白的增加和低密度脂蛋白的减少。APS 可抑制肝脏和脂肪组织中的脂质沉积。重要的是,APS 在体内不会损害肝脏和肾脏功能。为了探索 APS 对肥胖的有益作用是否来自于其对新陈代谢的影响,研究人员应用了代谢组学。不出所料,APS 处理后,高氟酸小鼠的代谢物谱发生了显著变化。其中,二磷酸尿苷葡萄糖(UDPG)是一种抑制脂肪酸生成的糖代谢中间产物,在 APS 的作用下显著上调。KEGG分析表明,APS处理的HFD小鼠的代谢物明显富集于不饱和脂肪酸的生物合成途径。为了进一步探究 APS 改变的代谢物是否会影响细胞的生物功能,研究人员进行了转录组学研究。GO 和 KEGG 分析显示,下调的基因组主要集中在脂质代谢方面。此外,负责细胞内脂质生成的内皮脂肪酶(LIPG)也是被 APS 显著抑制的基因之一。上述结果高度提示,APS 对脂质沉积的抑制可能与 UDPG 和 LIPG 密切相关。不出所料,在游离脂肪酸(FFA)诱导的肝细胞中,LIPG 水平受到 APS 的极大抑制。同样,糖原合成增加,而脂肪生成明显受到 APS 的抑制。此外,单独处理 UDPG 也会抑制 LIPG 的表达和脂肪生成。我们首次揭示了APS通过上调UDPG抑制LIPG,从而抑制了HFD喂养小鼠的脂肪生成,这表明APS可作为预防肥胖及其相关代谢疾病的临床和转化候选药物。
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来源期刊
CiteScore
26.00
自引率
21.40%
发文量
185
期刊介绍: Advanced Composites and Hybrid Materials is a leading international journal that promotes interdisciplinary collaboration among materials scientists, engineers, chemists, biologists, and physicists working on composites, including nanocomposites. Our aim is to facilitate rapid scientific communication in this field. The journal publishes high-quality research on various aspects of composite materials, including materials design, surface and interface science/engineering, manufacturing, structure control, property design, device fabrication, and other applications. We also welcome simulation and modeling studies that are relevant to composites. Additionally, papers focusing on the relationship between fillers and the matrix are of particular interest. Our scope includes polymer, metal, and ceramic matrices, with a special emphasis on reviews and meta-analyses related to materials selection. We cover a wide range of topics, including transport properties, strategies for controlling interfaces and composition distribution, bottom-up assembly of nanocomposites, highly porous and high-density composites, electronic structure design, materials synergisms, and thermoelectric materials. Advanced Composites and Hybrid Materials follows a rigorous single-blind peer-review process to ensure the quality and integrity of the published work.
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