{"title":"Astragalus polysaccharide inhibits lipogenesis in HFD-fed mice by suppressing LIPG via upregulation of UDPG","authors":"Xuelin Wang, Mengying Li, Fang Yu, Limin Hou, Rui Cao, Lei Zhang, Jianwu Xie, Feng Wang, Junrong Huang","doi":"10.1007/s42114-024-01046-7","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":7220,"journal":{"name":"Advanced Composites and Hybrid Materials","volume":"7 6","pages":""},"PeriodicalIF":23.2000,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Composites and Hybrid Materials","FirstCategoryId":"88","ListUrlMain":"https://link.springer.com/article/10.1007/s42114-024-01046-7","RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, COMPOSITES","Score":null,"Total":0}
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.
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.