Vitamin D Mitigates Hepatic Fat Accumulation and Inflammation and Increases SIRT1/AMPK Expression in AML-12 Hepatocytes
Emerging evidence has demonstrated a strong correlation between vitamin D status and fatty liver disease. Aberrant hepatic fat infiltration contributes to oxidant overproduction, promoting metabolic dysfunction, and inflammatory responses. Vitamin D supplementation might be a good strategy for reduc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/6/1401 |
| _version_ | 1797239864755748864 |
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| author | Eugene Chang |
| author_facet | Eugene Chang |
| author_sort | Eugene Chang |
| collection | DOAJ |
| description | Emerging evidence has demonstrated a strong correlation between vitamin D status and fatty liver disease. Aberrant hepatic fat infiltration contributes to oxidant overproduction, promoting metabolic dysfunction, and inflammatory responses. Vitamin D supplementation might be a good strategy for reducing hepatic lipid accumulation and inflammation in non-alcoholic fatty liver disease and its associated diseases. This study aimed to investigate the role of the most biologically active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D), in hepatic fat accumulation and inflammation in palmitic acid (PA)-treated AML-12 hepatocytes. The results indicated that treatment with 1,25(OH)2D significantly decreased triglyceride contents, lipid peroxidation, and cellular damage. In addition, mRNA levels of apoptosis-associated speck-like CARD-domain protein (ASC), thioredoxin-interacting protein (TXNIP), NOD-like receptor family pyrin domain-containing 3 (NLRP3), and interleukin-1β (IL-1β) involved in the NLRP3 inflammasome accompanied by caspase-1 activity and IL-1β expression were significantly suppressed by 1,25(OH)2D in PA-treated hepatocytes. Moreover, upon PA exposure, 1,25(OH)2D-incubated AML-12 hepatocytes showed higher sirtulin 1 (SIRT1) expression and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. A SIRT1 inhibitor alleviated the beneficial effects of 1,25(OH)2D on PA-induced hepatic fat deposition, IL-1β expression, and caspase-1 activity. These results suggest that the favorable effects of 1,25(OH)2D on hepatic fat accumulation and inflammation may be, at least in part, associated with the SIRT1. |
| first_indexed | 2024-04-24T17:58:19Z |
| format | Article |
| id | doaj.art-6c02e9ceca9441119ec7702049e1955a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-24T17:58:19Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6c02e9ceca9441119ec7702049e1955a2024-03-27T13:57:17ZengMDPI AGMolecules1420-30492024-03-01296140110.3390/molecules29061401Vitamin D Mitigates Hepatic Fat Accumulation and Inflammation and Increases SIRT1/AMPK Expression in AML-12 HepatocytesEugene Chang0Department of Food and Nutrition, Gangneung-Wonju National University, Gangneung-si 25457, Gangwon State, Republic of KoreaEmerging evidence has demonstrated a strong correlation between vitamin D status and fatty liver disease. Aberrant hepatic fat infiltration contributes to oxidant overproduction, promoting metabolic dysfunction, and inflammatory responses. Vitamin D supplementation might be a good strategy for reducing hepatic lipid accumulation and inflammation in non-alcoholic fatty liver disease and its associated diseases. This study aimed to investigate the role of the most biologically active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D), in hepatic fat accumulation and inflammation in palmitic acid (PA)-treated AML-12 hepatocytes. The results indicated that treatment with 1,25(OH)2D significantly decreased triglyceride contents, lipid peroxidation, and cellular damage. In addition, mRNA levels of apoptosis-associated speck-like CARD-domain protein (ASC), thioredoxin-interacting protein (TXNIP), NOD-like receptor family pyrin domain-containing 3 (NLRP3), and interleukin-1β (IL-1β) involved in the NLRP3 inflammasome accompanied by caspase-1 activity and IL-1β expression were significantly suppressed by 1,25(OH)2D in PA-treated hepatocytes. Moreover, upon PA exposure, 1,25(OH)2D-incubated AML-12 hepatocytes showed higher sirtulin 1 (SIRT1) expression and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. A SIRT1 inhibitor alleviated the beneficial effects of 1,25(OH)2D on PA-induced hepatic fat deposition, IL-1β expression, and caspase-1 activity. These results suggest that the favorable effects of 1,25(OH)2D on hepatic fat accumulation and inflammation may be, at least in part, associated with the SIRT1.https://www.mdpi.com/1420-3049/29/6/1401fat accumulationinflammationnon-alcoholic fatty liver disease (NAFLD)NOD-like receptor family pyrin domain-containing 3 (NLRP3)sirtulin 1 (SIRT1)vitamin D |
| spellingShingle | Eugene Chang Vitamin D Mitigates Hepatic Fat Accumulation and Inflammation and Increases SIRT1/AMPK Expression in AML-12 Hepatocytes Molecules fat accumulation inflammation non-alcoholic fatty liver disease (NAFLD) NOD-like receptor family pyrin domain-containing 3 (NLRP3) sirtulin 1 (SIRT1) vitamin D |
| title | Vitamin D Mitigates Hepatic Fat Accumulation and Inflammation and Increases SIRT1/AMPK Expression in AML-12 Hepatocytes |
| title_full | Vitamin D Mitigates Hepatic Fat Accumulation and Inflammation and Increases SIRT1/AMPK Expression in AML-12 Hepatocytes |
| title_fullStr | Vitamin D Mitigates Hepatic Fat Accumulation and Inflammation and Increases SIRT1/AMPK Expression in AML-12 Hepatocytes |
| title_full_unstemmed | Vitamin D Mitigates Hepatic Fat Accumulation and Inflammation and Increases SIRT1/AMPK Expression in AML-12 Hepatocytes |
| title_short | Vitamin D Mitigates Hepatic Fat Accumulation and Inflammation and Increases SIRT1/AMPK Expression in AML-12 Hepatocytes |
| title_sort | vitamin d mitigates hepatic fat accumulation and inflammation and increases sirt1 ampk expression in aml 12 hepatocytes |
| topic | fat accumulation inflammation non-alcoholic fatty liver disease (NAFLD) NOD-like receptor family pyrin domain-containing 3 (NLRP3) sirtulin 1 (SIRT1) vitamin D |
| url | https://www.mdpi.com/1420-3049/29/6/1401 |
| work_keys_str_mv | AT eugenechang vitamindmitigateshepaticfataccumulationandinflammationandincreasessirt1ampkexpressioninaml12hepatocytes |