Lingonberry Improves Hepatic Lipid Metabolism by Targeting Notch1 Signaling
Impaired hepatic lipid metabolism is a hallmark of non-alcoholic fatty liver disease (NAFLD), which has no effective treatment option. Recently, Notch signaling has been identified as an important mediator of hepatic lipid metabolism. Lingonberry (<i>Vaccinium vitis-idaea</i> L.) is an a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/3/472 |
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| author | Susara Madduma Hewage Kathy K. W. Au-Yeung Suvira Prashar Charith U. B. Wijerathne Karmin O Yaw L. Siow |
| author_facet | Susara Madduma Hewage Kathy K. W. Au-Yeung Suvira Prashar Charith U. B. Wijerathne Karmin O Yaw L. Siow |
| author_sort | Susara Madduma Hewage |
| collection | DOAJ |
| description | Impaired hepatic lipid metabolism is a hallmark of non-alcoholic fatty liver disease (NAFLD), which has no effective treatment option. Recently, Notch signaling has been identified as an important mediator of hepatic lipid metabolism. Lingonberry (<i>Vaccinium vitis-idaea</i> L.) is an anthocyanin-rich fruit with significant lipid-lowering properties. In this study, we examined how lingonberry influenced Notch signaling and fatty acid metabolism in a mouse model of NAFLD. Mice (C57BL/6J) fed a high-fat diet (HFD) for 12 weeks developed fatty liver and activated hepatic Notch1 signaling. Lingonberry supplementation inhibited hepatic Notch1 signaling and improved lipid profile by improving the expression of the genes involved in hepatic lipid metabolism. The results were verified using a palmitic-acid-challenged cell model. Similar to the animal data, palmitic acid impaired cellular lipid metabolism and induced Notch1 in HepG2 cells. Lingonberry extract or cyanidin-3-glucoside attenuated Notch1 signaling and decreased intracellular triglyceride accumulation. The inhibition of Notch in the hepatocytes attenuated sterol-regulatory-element-binding-transcription-factor-1 (<i>SREBP-1c)</i>-mediated lipogenesis and increased the expression of carnitine palmitoyltransferase-I-alpha (<i>CPTIα</i>) and acyl-CoA oxidase1 <i>(<i>ACOX1)</i>.</i> Taken together, lingonberry’s hepatoprotective effect is mediated by, in part, improving hepatic lipid metabolism via inhibiting Notch1 signaling in HFD-induced fatty liver. |
| first_indexed | 2024-03-09T13:53:37Z |
| format | Article |
| id | doaj.art-f4e5a8d76d6f4757bbd3f5ba4f7bd402 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T13:53:37Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-f4e5a8d76d6f4757bbd3f5ba4f7bd4022023-11-30T20:47:42ZengMDPI AGAntioxidants2076-39212022-02-0111347210.3390/antiox11030472Lingonberry Improves Hepatic Lipid Metabolism by Targeting Notch1 SignalingSusara Madduma Hewage0Kathy K. W. Au-Yeung1Suvira Prashar2Charith U. B. Wijerathne3Karmin O4Yaw L. Siow5Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB R2H 2A6, CanadaCanadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB R2H 2A6, CanadaCanadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB R2H 2A6, CanadaCanadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB R2H 2A6, CanadaCanadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB R2H 2A6, CanadaCanadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, MB R2H 2A6, CanadaImpaired hepatic lipid metabolism is a hallmark of non-alcoholic fatty liver disease (NAFLD), which has no effective treatment option. Recently, Notch signaling has been identified as an important mediator of hepatic lipid metabolism. Lingonberry (<i>Vaccinium vitis-idaea</i> L.) is an anthocyanin-rich fruit with significant lipid-lowering properties. In this study, we examined how lingonberry influenced Notch signaling and fatty acid metabolism in a mouse model of NAFLD. Mice (C57BL/6J) fed a high-fat diet (HFD) for 12 weeks developed fatty liver and activated hepatic Notch1 signaling. Lingonberry supplementation inhibited hepatic Notch1 signaling and improved lipid profile by improving the expression of the genes involved in hepatic lipid metabolism. The results were verified using a palmitic-acid-challenged cell model. Similar to the animal data, palmitic acid impaired cellular lipid metabolism and induced Notch1 in HepG2 cells. Lingonberry extract or cyanidin-3-glucoside attenuated Notch1 signaling and decreased intracellular triglyceride accumulation. The inhibition of Notch in the hepatocytes attenuated sterol-regulatory-element-binding-transcription-factor-1 (<i>SREBP-1c)</i>-mediated lipogenesis and increased the expression of carnitine palmitoyltransferase-I-alpha (<i>CPTIα</i>) and acyl-CoA oxidase1 <i>(<i>ACOX1)</i>.</i> Taken together, lingonberry’s hepatoprotective effect is mediated by, in part, improving hepatic lipid metabolism via inhibiting Notch1 signaling in HFD-induced fatty liver.https://www.mdpi.com/2076-3921/11/3/472nonalcoholic fatty liver disease (NAFLD)high-fat diet (HFD)lingonberrynotch signalinglipid metabolismpalmitic acid |
| spellingShingle | Susara Madduma Hewage Kathy K. W. Au-Yeung Suvira Prashar Charith U. B. Wijerathne Karmin O Yaw L. Siow Lingonberry Improves Hepatic Lipid Metabolism by Targeting Notch1 Signaling Antioxidants nonalcoholic fatty liver disease (NAFLD) high-fat diet (HFD) lingonberry notch signaling lipid metabolism palmitic acid |
| title | Lingonberry Improves Hepatic Lipid Metabolism by Targeting Notch1 Signaling |
| title_full | Lingonberry Improves Hepatic Lipid Metabolism by Targeting Notch1 Signaling |
| title_fullStr | Lingonberry Improves Hepatic Lipid Metabolism by Targeting Notch1 Signaling |
| title_full_unstemmed | Lingonberry Improves Hepatic Lipid Metabolism by Targeting Notch1 Signaling |
| title_short | Lingonberry Improves Hepatic Lipid Metabolism by Targeting Notch1 Signaling |
| title_sort | lingonberry improves hepatic lipid metabolism by targeting notch1 signaling |
| topic | nonalcoholic fatty liver disease (NAFLD) high-fat diet (HFD) lingonberry notch signaling lipid metabolism palmitic acid |
| url | https://www.mdpi.com/2076-3921/11/3/472 |
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