Effetto selettivo di sieri umani dislipidemici e degli acidi grassi poliinsaturi sull'espressione genica

Abstract

Serum profile, in physiological or pathological conditions, results from the whole effect of both nutritional intake and endogenous metabolism and is commonly used as diagnostic tool. Moreover individual serum components and their concentration are often related to specificity, development and progression of many metabolic diseases. Dietary fat intake strictly affects serum lipid profile and cardiovascular disease epidemiology. Fatty acids derived from diet, both saturated and polyunsaturated fatty acids, have specific and controversial effects. The underlying molecular mechanisms are numerous but partially understood, and they are related to homeostatic metabolic pathways as well gene expression effects. Consequently the aim of this project was to assess the ability of serum samples differing in content of nutritionally related lipid components to specifically affect gene expression of human hepatoma cells (HepG2). We collected 40 human sera, differing in metabolic and nutritionally relevant fatty acids, and tested their effect on hepatoma cells comparing samples from hyperlipidemic (cholesterol average 273 mg/dl) vs normolipidemic male subjects (cholesterol average 155 mg/dl). Analyzed genes were selected among those previously found modulated by lipid nutrients. Determination of fatty acids in sera showed that arachidonic acid (AA) was 88% more abundant in hypercholesterolemic subjects (p<0.01), while docosahexaneoic acid (DHA) and eicosopentanoic acid (EPA), as quota of total detected fatty acids, were significantly higher in normocholesterolemic subjects by 25% (p<0.05) and by 80% (p<0.01) respectively. Normocholesterolemic subjects had an higher n-3/n-6 fatty acids ratio (p<0.05). Hypercholesterolemic sera decreased sterol regulatory element binding protein-1c (SREBP-1c) mRNA by 40% (p<0.05). In hypercholesterolemic group ,UDP-glucuronosyltransferase-1A1 (UGT1A1) mRNA expression was significantly increased by 84% (p<0.01). Samples with higher concentrations of DHA, EPA and AA produced a higher expression of UGT1A1 mRNA. The amount of fatty acids, as c18:2, c18:3, DHA, EPA, AA, is more high in hypercholesterolemic subjects (p<0.01) and has an opposite trend compared to SREBP-1c mRNA expression (p<0.05). Our data clearly indicate that serum lipid profile is functionally linked with gene expression involved in metabolic and nutritional related conditions.[edited by author]