{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:52:22Z","timestamp":1790913142858,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFF1100103"],"award-info":[{"award-number":["2022YFF1100103"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["3207219"],"award-info":[{"award-number":["3207219"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["B18053"],"award-info":[{"award-number":["B18053"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2022YFF1100103"],"award-info":[{"award-number":["2022YFF1100103"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["3207219"],"award-info":[{"award-number":["3207219"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["B18053"],"award-info":[{"award-number":["B18053"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"111 Project from the Education Ministry of China","award":["2022YFF1100103"],"award-info":[{"award-number":["2022YFF1100103"]}]},{"name":"111 Project from the Education Ministry of China","award":["3207219"],"award-info":[{"award-number":["3207219"]}]},{"name":"111 Project from the Education Ministry of China","award":["B18053"],"award-info":[{"award-number":["B18053"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Short-chain fatty acids (SCFAs) are important metabolites of the intestinal flora that are closely related to the development of non-alcoholic fatty liver disease (NAFLD). Moreover, studies have shown that macrophages have an important role in the progression of NAFLD and that a dose effect of sodium acetate (NaA) on the regulation of macrophage activity alleviates NAFLD; however, the exact mechanism of action remains unclear. This study aimed to assess the effect and mechanism of NaA on regulating the activity of macrophages. RAW264.7 and Kupffer cells cell lines were treated with LPS and different concentrations of NaA (0.01, 0.05, 0.1, 0.5, 1, 1.5, 2, and 5 mM). Low doses of NaA (0.1 mM, NaA-L) significantly increased the expression of inflammatory factors tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-6 (IL-6), and interleukin 1 beta (IL-1\u03b2); it also increased the phosphorylation of inflammatory proteins nuclear factor-\u03baB p65 (NF-\u03baB p65) and c-Jun (p &lt; 0.05), and the M1 polarization ratio of RAW264.7 or Kupffer cells. Contrary, a high concentration of NaA (2 mM, NaA-H) reduced the inflammatory responses of macrophages. Mechanistically, high doses of NaA increased intracellular acetate concentration in macrophages, while a low dose had the opposite effect, consisting of the trend of changes in regulated macrophage activity. Besides, GPR43 and\/or HDACs were not involved in the regulation of macrophage activity by NaA. NaA significantly increased total intracellular cholesterol (TC), triglycerides (TG), and lipid synthesis gene expression levels in macrophages and hepatocytes at either high or low concentrations. Furthermore, NaA regulated the intracellular AMP\/ATP ratio and AMPK activity, achieving a bidirectional regulation of macrophage activity, in which the PPAR\u03b3\/UCP2\/AMPK\/iNOS\/I\u03baB\u03b1\/NF-\u03baB signaling pathway has an important role. In addition, NaA can regulate lipid accumulation in hepatocytes by NaA-driven macrophage factors through the above-mentioned mechanism. The results revealed that the mode of NaA bi-directionally regulating the macrophages further affects hepatocyte lipid accumulation.<\/jats:p>","DOI":"10.3390\/ijms24065536","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T06:14:58Z","timestamp":1678774498000},"page":"5536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Bidirectional Regulation of Sodium Acetate on Macrophage Activity and Its Role in Lipid Metabolism of Hepatocytes"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1539-1231","authenticated-orcid":false,"given":"Weiwei","family":"Li","sequence":"first","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"},{"name":"Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjuan","family":"Deng","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"},{"name":"Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Gong","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichao","family":"Hou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9244-3121","authenticated-orcid":false,"given":"Liang","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"},{"name":"Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"},{"name":"Research Center for Probiotics, China Agricultural University, Sanhe 065200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1007\/s10620-016-4049-x","article-title":"Innate immunity and inflammation in NAFLD\/NASH","volume":"61","author":"Arrese","year":"2016","journal-title":"Dig. 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