Chronic Microcystin-LR Exposure Induces Abnormal Lipid Metabolism via Endoplasmic Reticulum Stress in Male Zebrafish
In order to explore effects of low levels of continuous microcystin-LR (MC-LR) (a cyanotoxin) exposure on hepatic lipid metabolism on the basis of the endoplasmic reticulum stress (ERS) pathway, we exposed adult male zebrafish to MC-LR (0, 1, 5, and 25 μg/L) for 60 days, and hepatic histopa...
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MDPI AG
2020-02-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/12/2/107 |
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| author | Dandan Zhang Wang Lin Yinjie Liu Honghui Guo Lingkai Wang Liping Yang Li Li Dapeng Li Rong Tang |
| author_facet | Dandan Zhang Wang Lin Yinjie Liu Honghui Guo Lingkai Wang Liping Yang Li Li Dapeng Li Rong Tang |
| author_sort | Dandan Zhang |
| collection | DOAJ |
| description | In order to explore effects of low levels of continuous microcystin-LR (MC-LR) (a cyanotoxin) exposure on hepatic lipid metabolism on the basis of the endoplasmic reticulum stress (ERS) pathway, we exposed adult male zebrafish to MC-LR (0, 1, 5, and 25 μg/L) for 60 days, and hepatic histopathology as well as lipid metabolic parameters were determined with mRNA levels of ERS signal molecules and downstream factors, along with genes associated with lipid metabolism in zebrafish liver. The results revealed that prolonged exposure to MC-LR remarkably altered the levels of hepatic total cholesterol and triglyceride and led to hepatic steatosis, which was also confirmed by hepatic cytoplasmic vacuolization in Hematoxylin/eosin (H&E) stain and lipid droplet accumulation in Oil Red O stain. The severity of hepatic damage and lipidation was increased in a dose-related manner. MC-LR exposure significantly upregulated transcriptional levels of ERS markers including <i>hspa5</i>, <i>mapk8</i>, and <i>chop</i>, indicating the occurrence of ERS in the liver of zebrafish. Concurrently, MC-LR significantly improved mRNA expression of unfolded protein response (UPR) pathway-related genes including <i>atf6</i>, <i>eif2ak3</i>, <i>ern1</i>, and <i>xbp1s</i>, suggesting that all of the three UPR branches were activated by MC-LR. MC-LR also induced significant upregulation of downstream lipid metabolism-related factors and genes including <i>srebf1</i>, <i>srebf2</i>, fatty acid synthase (<i>fasn</i>), acetyl-CoA carboxylase (<i>acaca</i>), stearoyl-CoA desaturase (<i>scd</i>), HMG CoA reductase (<i>hmgcra</i>), and HMG CoA synthase (<i>hmgcs1</i>), and downregulation of genes associated with lipolysis such as triglyceride hydrolase gene (<i>atgl</i>), hormone-sensitive enzyme gene (<i>hsla</i>), and carnitine palmitoyltransferase gene (<i>cpt1aa</i>). Our present results indicated that the cause of hepatic lipid accumulation by MC-LR was mainly by upregulating lipogenic and cholesterol genes but downregulating the expression of lipolytic genes through the induction of <i>srebf1</i> and <i>srebf2</i>, which were involved in the activation of ERS signal pathways. |
| first_indexed | 2024-04-11T11:51:24Z |
| format | Article |
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| spelling | doaj.art-cf1d6d5ae60f4451903fcc35f7a308602022-12-22T04:25:19ZengMDPI AGToxins2072-66512020-02-0112210710.3390/toxins12020107toxins12020107Chronic Microcystin-LR Exposure Induces Abnormal Lipid Metabolism via Endoplasmic Reticulum Stress in Male ZebrafishDandan Zhang0Wang Lin1Yinjie Liu2Honghui Guo3Lingkai Wang4Liping Yang5Li Li6Dapeng Li7Rong Tang8College of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaIn order to explore effects of low levels of continuous microcystin-LR (MC-LR) (a cyanotoxin) exposure on hepatic lipid metabolism on the basis of the endoplasmic reticulum stress (ERS) pathway, we exposed adult male zebrafish to MC-LR (0, 1, 5, and 25 μg/L) for 60 days, and hepatic histopathology as well as lipid metabolic parameters were determined with mRNA levels of ERS signal molecules and downstream factors, along with genes associated with lipid metabolism in zebrafish liver. The results revealed that prolonged exposure to MC-LR remarkably altered the levels of hepatic total cholesterol and triglyceride and led to hepatic steatosis, which was also confirmed by hepatic cytoplasmic vacuolization in Hematoxylin/eosin (H&E) stain and lipid droplet accumulation in Oil Red O stain. The severity of hepatic damage and lipidation was increased in a dose-related manner. MC-LR exposure significantly upregulated transcriptional levels of ERS markers including <i>hspa5</i>, <i>mapk8</i>, and <i>chop</i>, indicating the occurrence of ERS in the liver of zebrafish. Concurrently, MC-LR significantly improved mRNA expression of unfolded protein response (UPR) pathway-related genes including <i>atf6</i>, <i>eif2ak3</i>, <i>ern1</i>, and <i>xbp1s</i>, suggesting that all of the three UPR branches were activated by MC-LR. MC-LR also induced significant upregulation of downstream lipid metabolism-related factors and genes including <i>srebf1</i>, <i>srebf2</i>, fatty acid synthase (<i>fasn</i>), acetyl-CoA carboxylase (<i>acaca</i>), stearoyl-CoA desaturase (<i>scd</i>), HMG CoA reductase (<i>hmgcra</i>), and HMG CoA synthase (<i>hmgcs1</i>), and downregulation of genes associated with lipolysis such as triglyceride hydrolase gene (<i>atgl</i>), hormone-sensitive enzyme gene (<i>hsla</i>), and carnitine palmitoyltransferase gene (<i>cpt1aa</i>). Our present results indicated that the cause of hepatic lipid accumulation by MC-LR was mainly by upregulating lipogenic and cholesterol genes but downregulating the expression of lipolytic genes through the induction of <i>srebf1</i> and <i>srebf2</i>, which were involved in the activation of ERS signal pathways.https://www.mdpi.com/2072-6651/12/2/107microcystin-lrzebrafishendoplasmic reticulum stresslipid metabolism |
| spellingShingle | Dandan Zhang Wang Lin Yinjie Liu Honghui Guo Lingkai Wang Liping Yang Li Li Dapeng Li Rong Tang Chronic Microcystin-LR Exposure Induces Abnormal Lipid Metabolism via Endoplasmic Reticulum Stress in Male Zebrafish Toxins microcystin-lr zebrafish endoplasmic reticulum stress lipid metabolism |
| title | Chronic Microcystin-LR Exposure Induces Abnormal Lipid Metabolism via Endoplasmic Reticulum Stress in Male Zebrafish |
| title_full | Chronic Microcystin-LR Exposure Induces Abnormal Lipid Metabolism via Endoplasmic Reticulum Stress in Male Zebrafish |
| title_fullStr | Chronic Microcystin-LR Exposure Induces Abnormal Lipid Metabolism via Endoplasmic Reticulum Stress in Male Zebrafish |
| title_full_unstemmed | Chronic Microcystin-LR Exposure Induces Abnormal Lipid Metabolism via Endoplasmic Reticulum Stress in Male Zebrafish |
| title_short | Chronic Microcystin-LR Exposure Induces Abnormal Lipid Metabolism via Endoplasmic Reticulum Stress in Male Zebrafish |
| title_sort | chronic microcystin lr exposure induces abnormal lipid metabolism via endoplasmic reticulum stress in male zebrafish |
| topic | microcystin-lr zebrafish endoplasmic reticulum stress lipid metabolism |
| url | https://www.mdpi.com/2072-6651/12/2/107 |
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