Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes

Abstract

Background and Aim: Studies have shown monounsaturated oleic acid to be less toxic than palmitic acid and to prevent/attenuate palmitic acid hepatocites toxicity in steatosis models in vitro. However, to what degree these effects are mediated by steatosis extent is unknown. Methods: We evaluated whether steatosis per se is associated with hepatocytes apoptosis and determined the role of oleic and palmitic acid, the most abundant fatty acids in western diets, on triglyceride accumulation and apoptosis in an in vitro model of steatosis induced in three hepatocytic cell lines (HepG2, HuH7, WRL68). The impact of incubation for 24 h with oleic (0.66 and 1.32 mM) and palmitic acid (0.33 and 0.66 mM), alone or combined (molar ratio 2 : 1) on steatosis, apoptosis, and insulin signalling, was evaluated. Results: Concurrent with PPARg and SREBP-1 gene activation, steatosis extent was larger when cells were treated with oleic than with palmitic acid; the latter fatty acid was associated with increased PPARa expression. Cell apoptosis was inversely proportional to steatosis deposition. Moreover, palmitic, but not oleic acid, impaired insulin signalling. Despite the higher amount of fat resulting from incubation of the two fatty acids combined, the apoptosis rate and impaired insulin signalling were lower than in cells treated with palmitic acid alone, indicating a protective effect of oleic acid. Conclusions: Oleic acid is more steatogenic but less apoptotic than palmitic acid in hepatocityc cell cultures. These data may provide a biological basis for clinical findings on dietary patterns and pathogenetic models of nonalcoholic fatty liver disease.

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

“…These data are in line with the role of PPARg in promoting lipid storage (Gavrilova et al 2003, Schadinger et al 2005. Moreover, in HepG2 cells, expression of PPARa was increased by palmitate (Ricchi et al 2009). Therefore, the absence of PPARa upregulation in lipid-loaded FaO cells may depend on the excess oleate versus palmitate (2:1) in the FFA mixture, and this excess oleate may also explain the decrease in the transcription of SCD1 observed in lipid-loaded FaO cells, since this enzyme synthesizes oleic acid.…”

Effects of individual and multiple fatty acids (palmitate, oleate and docosahaexenoic acid) on cell viability and lipid metabolism in LO2 human liver cells

“…As a saturated FA, PA effectively induces cell apoptosis compared with the mono-unsaturated OA. When the PA:OA ratio is 1:2, OA attenuates the apoptosis induced by PA (21). Similarly, the results of the present study demonstrated that OA ameliorated the inhibition of cell growth induced by high doses of PA and DHA.…”

High Fatty Diet Effects on Rat Liver

“…In another study, Ricchi et al (29) found that palmitic acid impaired insulin signalling. Despite the higher amount of fat resulting from incubation of the two fatty acids combined, the apoptosis rate and impaired insulin signalling were found lower than in cells treated with palmitic acid alone, indicating a protective effect of oleic acid (28).…”

“…Only Ricchi et al (29) found that oleic acid is protective against apoptosis, but more steatogenic than palmitic acid. One of the reason we couldn't find any significant differences between control group and high fat diet group, would be protective properties of omega-9 fatty acid.…”

“…The rats in the control group were on chow diet, rats on methionine cholinedeficient diet (MCDD), rats on MCDD enriched with olive oil, rats on MCDD with fish oil, rats on MCDD with butter fat. According to this study, olive oil decreases the accumulation of triglyceride in the liver of rats (29).…”