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In the current study, the crucial role of VD3 in maintaining energy homeostasis under short-term fasting conditions was investigated. Our results confirmed that glucose-depriving pathways were inhibited while glucose-producing pathways were strengthened in zebrafish after fasting for 24 or 48 h. Moreover, VD3 anabolism in zebrafish was significantly suppressed in a time-dependent manner under short-fasting conditions. After fasting for 24 or 48 h, zebrafish fed with VD3 displayed a higher gluconeogenesis level and lower glycolysis level in the liver, and the serum glucose was maintained at higher levels, compared to those fed without VD3. Additionally, VD3 augmented the expression of fatty acids (FAs) transporter cd36 and lipogenesis in the liver, while enhancing lipolysis in the dorsal muscle. Similar results were obtained in cyp2r1\u2212\/\u2212 zebrafish, in which VD3 metabolism is obstructed. Importantly, it was observed that VD3 induced the production of gut GLP-1, which is considered to possess a potent gluconeogenic function in zebrafish. Meanwhile, the gene expression of proprotein convertase subtilisin\/kexin type 1 (pcsk1), a GLP-1 processing enzyme, was also induced in the intestine of short-term fasted zebrafish. Notably, gut microbiota and its metabolite acetate were involved in VD3-regulated pcsk1 expression and GLP-1 production under short-term fasting conditions. In summary, our study demonstrated that VD3 regulated GLP-1 production in zebrafish by influencing gut microbiota and its metabolite, contributing to energy homeostasis and ameliorating hypoglycemia under short-term fasting conditions.<\/jats:p>","DOI":"10.3390\/nu16091271","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T05:26:13Z","timestamp":1714022773000},"page":"1271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vitamin D3 Regulates Energy Homeostasis under Short-Term Fasting Condition in Zebrafish (Danio Rerio)"],"prefix":"10.3390","volume":"16","author":[{"given":"Qingyang","family":"Du","sequence":"first","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1774-6461","authenticated-orcid":false,"given":"Rui","family":"Shao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6052-0786","authenticated-orcid":false,"given":"Xinmeng","family":"Liao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Yin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghui","family":"Ai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangsen","family":"Mai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4629-9306","authenticated-orcid":false,"given":"Min","family":"Wan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev.physiol.68.040104.105739","article-title":"The Comparative Physiology of Food Deprivation: From Feast to Famine","volume":"68","author":"Wang","year":"2006","journal-title":"Annu. 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