Polyphenol-rich black chokeberry (Aronia melanocarpa) extract regulates the expression of genes critical for intestinal cholesterol flux in Caco-2 cells

Abstract

Black chokeberry (Aronia melanocarpa) is a rich source of polyphenols. The hypolipidemic effects of polyphenol-rich black chokeberry extract (CBE) have been reported, but underlying mechanisms have not been well characterized. We investigated the effect of CBE on the expression of genes involved in intestinal lipid metabolism. Caco-2 cells were incubated with 50 or 100 μg/ml of CBE for 24 h for quantitative realtime polymerase chain reaction analysis. Expression of genes for cholesterol synthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase and sterol regulatory element binding protein 2), apical cholesterol uptake (Niemann-Pick C1 Like 1 and scavenger receptor class B Type 1) and basolateral cholesterol efflux [ATP-binding cassette transporter A1 (ABCA1)] was significantly decreased by CBE compared with control. Western blot analysis confirmed that CBE inhibited expression of these proteins. In contrast, CBE markedly induced mRNA and/or protein levels of ABCG5 and ABCG8 that mediate apical cholesterol efflux to the intestinal lumen. Furthermore, CBE significantly increased mRNA and protein levels of low-density lipoprotein (LDL) receptor, and cellular LDL uptake. Expression of genes involved in lipid metabolism and lipoprotein assembly, including sterol regulatory element-binding protein 1c, fatty acid synthase and acyl-CoA oxidase 1, was significantly decreased by CBE in a dose-dependent manner. Concomitantly, CBE significantly increased sirtuin 1, 3 and 5 mRNA levels, while it decreased SIRT-2. Our data suggest that hypolipidemic effects of CBE may be attributed, at least in part, to increased apical efflux of LDL-derived cholesterol and to decreased chylomicron formation in the intestine; and specific isoforms of SIRT may play an important role in this process.

Keywords: 3-hydroxy-3-methylglutaryl coenzyme A reductase; ABCA1; ABCG5/8; ACOX-1; ATP binding cassette transporter A1; ATP binding cassette transporter G5/8; CPT-1α; CVD; Caco-2 cells; Chokeberry; FAS; HMGR; LDL receptor; LDLR; PPARα; ROS; SCAP; SCD-1; SIRT; SR-BI; SREBP; SREBP cleavage-activating protein; TICE; Transintestinal cholesterol efflux; acyl-CoA oxidase 1; cardiovascular disease; carnitine palmitoyltransferase 1α; fatty acid synthase; peroxisome proliferator activated receptor α; reactive oxygen species; scavenger receptor class B, Type I; sirtuin; stearoyl-CoA desaturase 1; sterol regulatory element binding protein; transintestinal cholesterol efflux.