{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:26:34Z","timestamp":1788852394661,"version":"build-2803163510"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Atherosclerotic cardiovascular disease has a high mortality worldwide. Our lab previously purified a polysaccharide designated as CM1 with (1\u21924)-\u03b2-D-Glc<jats:italic>p<\/jats:italic> and (1\u21922)-\u03b1-D-Man<jats:italic>p<\/jats:italic> glycosyls as the backbone. In this study, we investigated the anti-atherosclerosis effect of CM1 and the underlying mechanisms of action in a low-density lipoprotein receptor knockout (LDLR<jats:sup>(-\/-)<\/jats:sup> mouse model. It was found that CM1 significantly decreased the formation of atherosclerotic plaques. Mechanistically, CM1 enhanced plasma level of apolipoprotein A-I and decreased the plasma levels of triglyceride, apolipoprotein B, and total cholesterol. In the absence of LDLR, CM1 elevated the expression of very low-density lipoprotein receptor for liver uptake of plasma apolipoprotein B-containing particles and reduced hepatic triglyceride synthesis by inhibiting sterol regulatory element binding protein 1c. CM1 improved lipids excretion by increasing the liver X receptor \u03b1\/ATP-binding cassette G5 pathway in small intestine. CM1 reduced lipogenesis and lipolysis by inhibiting peroxisome proliferator-activated receptor <jats:italic>\u03b3<\/jats:italic> and adipose triglyceride lipase in epididymal fat. Furthermore, CM1 improved lipid profile in C57BL\/6J mice. Collectively, CM1 can modulate lipid metabolism by multiple pathways, contributing to reduced plasma lipid level and formation of atherosclerotic plaques in LDLR<jats:sup>(\u2212\/\u2212)<\/jats:sup> mice. This molecule could be explored as a potential compound for prevention and treatment of hyperlipidemia and atherosclerosis.<\/jats:p>","DOI":"10.3389\/fmolb.2021.783807","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T08:24:38Z","timestamp":1639383878000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["The Cordyceps militaris-Derived Polysaccharide CM1 Alleviates Atherosclerosis in LDLR(-\/-) Mice by Improving Hyperlipidemia"],"prefix":"10.3389","volume":"8","author":[{"given":"Fan","family":"Yin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Qian","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuo","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shou-Dong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1126\/science.271.5248.518","article-title":"Identification of Scavenger Receptor SR-BI as a High Density Lipoprotein Receptor","volume":"271","author":"Acton","year":"1996","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1097\/MOL.0000000000000676","article-title":"Regulation of Lipoprotein Lipase-Mediated Lipolysis of Triglycerides","volume":"31","author":"Basu","year":"2020","journal-title":"Curr. 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