Effect of dietary fish oil on fatty acid deposition and expression of cholesterol homeostasis controlling genes in the liver and plasma lipid profile: comparison of two animal models
On the other hand, dietary n‐3 long‐chain polyunsaturated fatty acids (LC‐PUFA n‐3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are known to decrease plasma TAG via activation of PPARα (peroxisome proliferator‐activated receptor α) and inhibition of SREBP‐1 (sterol response element‐binding protein 1) signalling pathways; this stimulates fatty acid (FA) β‐oxidation and inhibits FA synthesis (Jump, 2008). However, results of the studies evaluating EPA/DHA effects on plasma TC, LDLC and HDLC are often contradictory (Eslick et al., 2009).
Expression of the genes coding for the key proteins controlling cholesterol homeostasis, hepatic 3‐hydroxy‐3‐methyl‐glutaryl‐CoA reductase (HMG‐CoA‐R) and low‐density lipoprotein receptor (LDL‐R) is stimulated by the transcription factor SREBP‐2, whose activation is affected by the INSIG protein (insulin‐induced gene), product of the Insig gene (Sato, 2010). Moreover, SREBP‐2 activation is presumably related to PPARα ligation by EPA/DHA (Luci et al., 2007a,b).
In vivo studies testing EPA/DHA effect on plasma lipids are usually carried out on rodents (Arai et al., 2009; Lu et al., 2011; Takahashi, 2011; Yamazaki et al., 2011). However, regarding the above‐mentioned inclusion of the transcription factor PPARα in the pertinent signalling pathways, rodents (in this context ‘proliferating’ species) are not ideal models for humans (‘non‐proliferating’ species, together, e.g., with pigs; Komprda, 2012).
The objective of the present study was to compare two animal models, rat and pig, regarding an effect of fish oil (the most common source of EPA+DHA) on hepatic fatty acid deposition, on expression in the liver of the genes presumably affecting cholesterol homeostasis and on plasma lipid level. An intention was to carry out an experiment as similar to usual human conditions as possible (fish oil ingested as an integral feed component without the application of a gavage) and to use dietary EPA+DHA (fish oil) in the amount realistically achievable in human nutrition.