{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:29:43Z","timestamp":1792096183218,"version":"4.4.0"},"reference-count":74,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jilin Province Innovative and Entrepreneurial Talent Funding Project of Jilin Human Resources and Social Security Department","award":["2023RY16"],"award-info":[{"award-number":["2023RY16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Globally, metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), is one of the most common liver disorders and is strongly associated with copper deficiency. To explore the potential effects and mechanisms of Lactiplantibacillus plantarum LPJZ-658, copper deficiency combined with a high-sugar diet-induced MASLD mouse model was utilized in this study. We fed 40-week-old (middle-aged) male C57BL\/6 mice a copper-deficient and high-sugar diet for 16 weeks (CuDS), with supplementary LPJZ-658 for the last 6 weeks (CuDS + LPJZ-658). In this study, we measured body weight, liver weight, and serum biochemical markers. Lipid accumulation, histology, lipidomics, and sphingolipid metabolism-related enzyme expression were investigated to analyze liver function. Untargeted metabolomics was used to analyze the serum and the composition and abundance of intestinal flora. In addition, the correlation between differential liver lipid profiles, serum metabolites, and gut flora at the genus level was measured. The results show that LPJZ-658 significantly improves abnormal liver function and hepatic steatosis. The lipidomics analyses and metabolic pathway analysis identified sphingolipid, retinol, and glycerophospholipid metabolism as the most relevant metabolic pathways that characterized liver lipid dysregulation in the CuDS group. Consistently, RT-qPCR analyses revealed that the enzymes catalyzing sphingolipid metabolism that were significantly upregulated in the CuDS group were downregulated by the LPJZ-658 treatment. In addition, the serum metabolomics results indicated that the linoleic acid, taurine and hypotaurine, and ascorbate and aldarate metabolism pathways were associated with CuDS-induced MASLD. Notably, we found that treatment with LPJZ-658 partially reversed the changes in the differential serum metabolites. Finally, LPJZ-658 effectively regulated intestinal flora abnormalities and was significantly correlated with differential hepatic lipid species and serum metabolites. In conclusion, we elucidated the function and potential mechanisms of LPJZ-658 in alleviating copper deficiency combined with sugar-induced middle-aged MASLD and hope this will provide possible treatment strategies for improving MASLD.<\/jats:p>","DOI":"10.3390\/nu16132010","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T10:10:07Z","timestamp":1719310207000},"page":"2010","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exploring the Regulatory Effect of LPJZ-658 on Copper Deficiency Combined with Sugar-Induced MASLD in Middle-Aged Mice Based on Multi-Omics Analysis"],"prefix":"10.3390","volume":"16","author":[{"given":"Chunhua","family":"Li","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City 132101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City 132101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City 132101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lichun","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City 132101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2582-7480","authenticated-orcid":false,"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Changchun Veterinary Research Institute, Chinese Academy of Medical Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City 132101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7866-3160","authenticated-orcid":false,"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Changchun Veterinary Research Institute, Chinese Academy of Medical Sciences, Changchun 130122, China"},{"name":"Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0095-2573","authenticated-orcid":false,"given":"Cuiqing","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City 132101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1001\/jama.2015.5370","article-title":"Nonalcoholic fatty liver disease: A systematic review","volume":"313","author":"Rinella","year":"2015","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Medina-Santillan, R., Lopez-Velazquez, J.A., Chavez-Tapia, N., Torres-Villalobos, G., Uribe, M., and Mendez-Sanchez, N. 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