Influence of Resveratrol on Sphingolipid Metabolism in Hepatocellular Carcinoma Cells in Lipid Overload State.

Abstract:

BACKGROUND:Obesity is characterized by increased long chain fatty acids (LCFA) uptake and impaired lipid metabolism in hepatocytes. Consequently, an enhanced intracellular lipid content, including sphingolipids, may lead to lipotoxicity. It is believed that resveratrol (RSV), one of the most extensively studied plant-derived polyphenols, and its interaction with sphingolipid metabolism may constitute one of the major therapeutic targets for cancer and metabolic diseases treatment. OBJECTIVE:The aim of this study was to ascertain, whether resveratrol may affect sphingolipid metabolic pathways, enzymes and transporters in a lipid overload state. METHODS:The experiments were conducted on hepatocellular carcinoma cells (HepG2) incubated with RSV and/or Palmitic Acid (PA) at the concentration of 0.5 mM and 50 µM, respectively for 16h. Intra- and extracellular sphingolipid concentrations were assessed by high-performance liquid chromatography and gas liquid chromatography. Moreover, the expression of caspase 3, selected fatty acid transporters and sphingolipid metabolism pathway proteins were estimated by Western Blot. RESULTS:RSV alone and together with PA significantly increased the intracellular concentration of ceramide, sphinganine and sphingosine as well as the expression of enzymes related to de novo ceramide synthesis pathway. Moreover, in our study, we observed augmented ceramide and sphingomyelin efflux into the incubation media in these groups. In addition, RSV substantially reduced intracellular triacylglycerols accumulation in lipid overload conditions. CONCLUSION:The above-mentioned findings suggest that RSV, at least partially, demonstrates a potential protective effect on HepG2 cells in a lipid overload state.

authors

Charytoniuk T,Harasim-Symbor E,Polak A,Drygalski K,Berk K,Chabowski A,Konstantynowicz-Nowicka K

doi

10.2174/1871520619666181224161255

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

121-129

issue

1

eissn

1871-5206

issn

1875-5992

pii

ACAMC-EPUB-95420

journal_volume

19

pub_type

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