PMID- 38474201 OWN - NLM STAT- MEDLINE DCOM- 20240314 LR - 20240315 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 5 DP - 2024 Mar 3 TI - Hypolipidemic Effect of Rice Bran Oil Extract Tocotrienol in High-Fat Diet-Induced Hyperlipidemia Zebrafish (Danio Rerio) Induced by High-Fat Diet. LID - 10.3390/ijms25052954 [doi] LID - 2954 AB - In recent years, the potent influence of tocotrienol (T3) on diminishing blood glucose and lipid concentrations in both Mus musculus (rats) and Homo sapiens (humans) has been established. However, the comprehensive exploration of tocotrienol's hypolipidemic impact and the corresponding mechanisms in aquatic species remains inadequate. In this study, we established a zebrafish model of a type 2 diabetes mellitus (T2DM) model through high-fat diet administration to zebrafish. In the T2DM zebrafish, the thickness of ocular vascular walls significantly increased compared to the control group, which was mitigated after treatment with T3. Additionally, our findings demonstrate the regulatory effect of T3 on lipid metabolism, leading to the reduced synthesis and storage of adipose tissue in zebrafish. We validated the expression patterns of genes relevant to these processes using RT-qPCR. In the T2DM model, there was an almost two-fold upregulation in ppargamma and cyp7a1 mRNA levels, coupled with a significant downregulation in cpt1a mRNA (p < 0.01) compared to the control group. The ELISA revealed that the protein expression levels of Ppargamma and Rxralpha exhibited a two-fold elevation in the T2DM group relative to the control. In the T3-treated group, Ppargamma and Rxralpha protein expression levels consistently exhibited a two-fold decrease compared to the model group. Lipid metabolomics showed that T3 could affect the metabolic pathways of zebrafish lipid regulation, including lipid synthesis and decomposition. We provided experimental evidence that T3 could mitigate lipid accumulation in our zebrafish T2DM model. Elucidating the lipid-lowering effects of T3 could help to minimize the detrimental impacts of overfeeding in aquaculture. FAU - Liu, Naicheng AU - Liu N AD - Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. FAU - Zhang, Peng AU - Zhang P AD - Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. FAU - Xue, Mingyang AU - Xue M AUID- ORCID: 0000-0003-3370-5712 AD - Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. FAU - Zhang, Mengwei AU - Zhang M AD - Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. FAU - Huang, Zhenyu AU - Huang Z AD - Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. FAU - Xu, Chen AU - Xu C AUID- ORCID: 0000-0002-5075-7154 AD - Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. FAU - Meng, Yan AU - Meng Y AD - Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. FAU - Fan, Yuding AU - Fan Y AUID- ORCID: 0000-0002-7291-2493 AD - Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. FAU - Liu, Wei AU - Liu W AD - Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. FAU - Zhang, Feixiang AU - Zhang F AD - Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. AD - College of Fisheries and Life, Shanghai Ocean University, Shanghai 201306, China. FAU - Chen, Peng AU - Chen P AD - Institute of Fishery Research of Xinjiang Uygur Autonenous Region, Urumqi 830099, China. FAU - Zhou, Yong AU - Zhou Y AUID- ORCID: 0000-0003-0373-5734 AD - Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. LA - eng GR - 2022BBA0054, 2023BBB122/CARS-45, technical innovation special project of Hubei Province/ GR - 32202980/the national natural science foundation of China/ GR - 2023TD46, YFI 202207/central public-interest scientific institution basal research fund/ PT - Journal Article DEP - 20240303 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Tocotrienols) RN - LZO6K1506A (Rice Bran Oil) RN - 0 (PPAR gamma) RN - 0 (RNA, Messenger) SB - IM MH - Humans MH - Mice MH - Rats MH - Animals MH - *Tocotrienols/metabolism MH - Zebrafish/metabolism MH - Diet, High-Fat MH - *Hyperlipidemias/metabolism MH - Rice Bran Oil MH - *Diabetes Mellitus, Type 2/metabolism MH - PPAR gamma/metabolism MH - RNA, Messenger/metabolism MH - Lipid Metabolism MH - Liver/metabolism PMC - PMC10931685 OTO - NOTNLM OT - blood fat OT - high-fat diet OT - rice bran oil extract OT - tocotrienol (T3) OT - type 2 diabetes mellitus (T2DM) model OT - zebrafish COIS- The authors declare no conflict of interest. EDAT- 2024/03/13 06:46 MHDA- 2024/03/14 06:47 PMCR- 2024/03/03 CRDT- 2024/03/13 01:24 PHST- 2024/01/18 00:00 [received] PHST- 2024/02/23 00:00 [revised] PHST- 2024/02/24 00:00 [accepted] PHST- 2024/03/14 06:47 [medline] PHST- 2024/03/13 06:46 [pubmed] PHST- 2024/03/13 01:24 [entrez] PHST- 2024/03/03 00:00 [pmc-release] AID - ijms25052954 [pii] AID - ijms-25-02954 [pii] AID - 10.3390/ijms25052954 [doi] PST - epublish SO - Int J Mol Sci. 2024 Mar 3;25(5):2954. doi: 10.3390/ijms25052954.