ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P912 | DOI: 10.1530/endoabs.63.P912

1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and lipid accumulation in liver cells: A role for epigenetic mechanisms?

Francisca Salas Perez1, J Alfredo Martinez1,2,3 & Fermín I Milagro1,2,3

1Department of Nutrition, Food Science and Physiology; Center for Nutrition Research, University of Navarra, Pamplona, Spain; 2IdiSNA, Navarra Institute for Health Research, Pamplona, Spain; 3CIBERobn, Fisiopatología de la Obesidad y la Nutrición, Carlos III Health Institute, Madrid, Spain.

Context: Vitamin D is a fat-soluble vitamin which requires the hydroxylation into 1,25-dihydroxyvitamin D (1,25-(OH)2D3) to be fully active. Vitamin D deficiency is a worldwide health problem associated to a wide range of acute and chronic diseases. On other hand, vitamin D supplementation has been proposed to reduced the risk of metabolic dysfunctions including obesity, type 2 diabetes and cardiovascular disease. Vitamin D interacts with the epigenetic machinery on multiple levels, but little is known about those regulatory mechanisms where vitamin D is involved.

Aim: To analyze the effects of 1,25-dihydroxyvitamin D on lipid accumulation and epigenetic changes in a human liver cell line.

Design: Lipid accumulation was induced in HepG2 cells by treating with a mixture of fatty acids (oleic acid and palmitic acid; 1 mM). To study the potential prevention of lipid accumulation, cells were also exposed to 1,25-(OH)2D3 (25, 100 and 250 pM) for 24 hours. In a second approach, to analyze if 1,25-(OH)2D3 could reverse lipid accumulation, cells were pre-incubated with fatty acids for 24 hours and then, were treated with 1,25-(OH)2D3. Cell viability was determined using MTS, lipid content was measured with Nile Red Stain, and expression of genes involved in lipid metabolism (ACOX1, PPARA, SREBP1, GPAM, FASN, TET1, TET2) were quantified by qRT-PCR by using specific probes.

Results: Treatment with 1,25-(OH)2D3 for 24 hours did not affect cell viability. The simultaneous exposure to 1,25-(OH)2D3 and fatty acids showed a trend to a decrease in lipid accumulation without changes in classic metabolic genes, but the expression of TET1 and TET2, key enzymes in DNA methylation, was down-regulated. The exposure to 1,25-(OH)2D3, after the fatty acids load, increased lipid accumulation in a dose response manner. This increase in fat deposition was associated with a reduction in mRNA levels of ACOX1, PPARA, SREBP1, and FASN.

Conclusion: The exposure to 1,25-(OH)2D3 and fatty acids induced changes in lipid accumulation associated to a differential gene expression that requires further analysis to evaluate the participation of epigenetic mechanisms. Indeed 1,25-(OH)2D3 might contribute to reduce liver fat accumulation, although it could have detrimental effects when hepatic steatosis is already present.

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