fat-1 transgenic zebrafish are protected from abnormal lipid deposition induced by high-vegetable oil feeding

Sun, Shouxiang; Castro, L. Filipe C.; Monroig, Óscar; Cao, Xiaojuan; Gao, Jian

doi:10.1007/s00253-020-10774-x

Cited by 10 publications

(11 citation statements)

References 46 publications

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“…A high vacuolization tendency has been observed in the liver of 16 to 22-month-old zebrafish fed 5% dietary lipid (99). Furthermore, lipid and glycogen vacuolization has also been observed in previous studies wherein zebrafish were fed 11 to 13% lipids (100,101). The low cholesterol diet in our study with 12% lipid also led to lipid accumulation in the liver of zebrafish.…”

Section: Cholesterol and β-Glucans Affected Vacuolization In The Liver And Micromorphology Of The Intestinesupporting

confidence: 87%

Management of Hypercholesterolemia Through Dietary ß-glucans–Insights From a Zebrafish Model

et al. 2022

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Consumption of lipid-rich foods can increase the blood cholesterol content. β-glucans have hypocholesterolemic effect. However, subtle changes in their molecular branching can influence bioactivity. Therefore, a comparative investigation of the cholesterol-lowering potential of two β-glucans with different branching patterns and a cholesterol-lowering drug, namely simvastatin was undertaken employing the zebrafish (Danio rerio) model of diet-induced hypercholesterolemia. Fish were allocated to 5 dietary treatments; a control group, a high cholesterol group, two β-glucan groups, and a simvastatin group. We investigated plasma total cholesterol, LDL and HDL cholesterol levels, histological changes in the tissues, and explored intestinal transcriptomic changes induced by the experimental diets. Dietary cholesterol likely caused the suppression of endogenous cholesterol biosynthesis, induced dysfunction of endoplasmic reticulum and mitochondria, and altered the histomorphology of the intestine. The two β-glucans and simvastatin significantly abated the rise in plasma cholesterol levels and restored the expression of specific genes to alleviate the endoplasmic reticulum-related effects induced by the dietary cholesterol. Furthermore, the distinct patterns of transcriptomic changes in the intestine elicited by the oat and microalga β-glucans impacted processes such as fatty acid metabolism, protein catabolic processes, and nuclear division. Oat and microalgal β-glucans also altered the pattern of lipid deposition in the liver. Our study provides insights into the effectiveness of different β-glucans to alleviate dysfunctions in lipid metabolism caused by dietary cholesterol.

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Section: Cholesterol and β-Glucans Affected Vacuolization In The Liver And Micromorphology Of The Intestinesupporting

confidence: 87%

Management of Hypercholesterolemia Through Dietary ß-glucans–Insights From a Zebrafish Model

et al. 2022

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“…As an n-3 PUFA desaturase, fat-1 transgenes have been shown to significantly alter ratio of n-6: n-3 PUFA by converting n-6 PUFA to n-3 PUFA in mice ( Kang. 2007 ), pigs ( Pan et al, 2010 ; Tang et al, 2014 ; Liu et al, 2016 ), cows ( Wu et al, 2012 ), sheep ( Duan et al, 2012 ), and zebrafish ( Sun et al, 2020 ). A similar phenomenon was also observed in this study.…”

Section: Discussionmentioning

confidence: 99%

“…In this way, changes in n-3 PUFA content may have more effects on the body. Studies have shown that fat-1 transgenes regulate energy metabolism by downregulating the ratio of n-6: n-3 PUFA ( Hagopian et al, 2010 ; Sun et al, 2020 ). Moreover, PUFA act as a substrate for energy metabolism and signaling molecules, which can also regulate gene expression ( Jump.…”

Section: Discussionmentioning

confidence: 99%

“…Obulesu et al reported dietary supplementation with squalene and PUFA significantly attenuated age-associated inhibition on mitochondrial TCA cycle enzyme activity, including ICDHm, α-KGDH, SDH, MDH, and mitochondrial complex I, which maintained hepatic energy status at near normal levels ( Obulesu et al, 2014 ). In fat-1 transgenic mice, activity of complex I was weakened, and the products of the TCA cycle also decreased ( Sun et al, 2020 ). The present data indicated that, in the fat-1 transgene cells, products from glycolysis (glucose, PA and CA), the key limiting enzymes in TCA cycle (IDHm, SDH, and MDHm), and key enzymes in OXPHOS were all downregulated.…”

Section: Discussionmentioning

confidence: 99%

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N-3 Polyunsaturated Fatty Acid Dehydrogenase Fat-1 Regulates Mitochondrial Energy Metabolism by Altering DNA Methylation in Isolated Cells of Transgenic Cattle

Wang

Zhu

Wei

et al. 2022

Front. Mol. Biosci.

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The fatty acid dehydrogenase fat-1 gene, derived from Caenorhabditis elegans, encodes n-3 polyunsaturated fatty acid dehydrogenase (Δ15 desaturase) and catalyzes the 18–20-carbon n-6 polyunsaturated fatty acids (n-6 PUFA) to generate corresponding n-3 polyunsaturated fatty acids (n-3 PUFA). Subsequently, fat-1 can influence the n-6: n-3 PUFA ratio in fat-1 transgenic cells. This study aimed to explore which processes of energy metabolism are affected exogenous fat-1 transgene and the relationship between these effects and DNA methylation. Compared with the wild-type group, the n-3 PUFA content in fat-1 transgenic bovine fetal fibroblasts was significantly increased, and the n-6 PUFA content and the n-6: n-3 PUFA ratio decreased. In the context of energy metabolism, the increase of exogenous fat-1 transgene decreased ATP synthesis by 39% and reduced the activity and expression of key rate-limiting enzymes in glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation, thus weakening the cells’ capacity for ATP production. DNA methylation sequencing indicated that this inhibition of gene expression may be due to altered DNA methylation that regulates cell energy metabolism. Exogenous fat-1 transgenic cells showed changes in the degree of methylation in the promoter region of genes related to energy metabolism rate-limiting enzymes. We suggest that alters the balance of n-6/n-3 PUFA could regulate altered DNA methylation that affect mitochondrial energy metabolism.

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“…Previous research has indicated that a lack of ∆5 desaturase activity impairs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) synthesis in Red Sea bream and Japanese flounder cells ( Nyunoya et al, 2021 ). Transgenic zebrafish and common carp enriched in n-3 fatty acids are protected from abnormal lipid deposition in the liver ( Pang et al, 2014 ; Sun et al, 2020a ; Zhang et al, 2019 ). Zebrafish are considered an important model for studying lipogenesis and fatty liver disease ( Hölttä-Vuori et al, 2010 ; Quinlivan & Farber, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Depletion of <i>stearoyl-CoA desaturase</i> (<i>scd</i>) leads to fatty liver disease and defective mating behavior in zebrafish

Wang

et al. 2023

Zoological Research

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Stearyl coenzyme A desaturase (SCD), also known as delta-9 desaturase, catalyzes the rate-limiting step in the formation of monounsaturated fatty acids. In mammals, depletion or inhibition of SCD activity generally leads to a decrease in triglycerides and cholesteryl esters. However, the endogenous role of scd in teleost fish remains unknown. Here, we generated a zebrafish scd mutant ( scd -/- ) to elucidate the role of scd in lipid metabolism and sexual development. Gas chromatography-mass spectrometry (GC-MS) showed that the scd -/- mutants had increased levels of saturated fatty acids C16:0 and C18:0, and decreased levels of monounsaturated fatty acids C16:1 and C18:1. The mutant fish displayed a short stature and an enlarged abdomen during development. Unlike Scd -/- mammals, the scd -/- zebrafish showed significantly increased fat accumulation in the whole body, especially in the liver, leading to hepatic mitochondrial dysfunction and severe cell apoptosis. Mechanistically, srebf1 , a gene encoding a transcriptional activator related to adipogenesis, acc1 and acaca , genes involved in fatty acid synthesis, and dgat2 , a key gene involved in triglyceride synthesis, were significantly upregulated in mutant livers to activate fatty acid biosynthesis and adipogenesis. The scd -/- males exhibited defective natural mating behavior due to defective genital papillae but possessed functional mature sperm. All defects in the scd -/- mutants could be rescued by ubiquitous transgenic overexpression of scd . In conclusion, our study demonstrates that scd is indispensable for maintaining lipid homeostasis and development of secondary sexual characteristics in zebrafish.

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fat-1 transgenic zebrafish are protected from abnormal lipid deposition induced by high-vegetable oil feeding

Cited by 10 publications

References 46 publications

Management of Hypercholesterolemia Through Dietary ß-glucans–Insights From a Zebrafish Model

Management of Hypercholesterolemia Through Dietary ß-glucans–Insights From a Zebrafish Model

N-3 Polyunsaturated Fatty Acid Dehydrogenase Fat-1 Regulates Mitochondrial Energy Metabolism by Altering DNA Methylation in Isolated Cells of Transgenic Cattle

Depletion of <i>stearoyl-CoA desaturase</i> (<i>scd</i>) leads to fatty liver disease and defective mating behavior in zebrafish

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