It has been reported that chronic stress, combined with high-fat/high-sugar diet, causes metabolic syndrome by neuropeptide Y (NPY) through NPY Y2 receptor (Y2R). We have previously reported the causal relation between serum HDL-cholesterol levels and single nucleotide polymorphisms (SNPs) on the regulatory region of Y2R gene. This study aims to investigate whether drug or ingredients of foods with anti-atherosclerotic functions influence Y2R gene expression through which NPY might promote atherosclerosis in HepG2 and prevent it in macrophages. Effect of varying ingredients of foods or drugs on mRNA levels of Y2R in cultured HepG2 or on mRNA levels of ABCA1, ABCG1 and Y2R in cultured THP-1-derived macrophages was examined by using real time PCR methods. Chlorogenic acid (CGA) and zeaxanthin significantly upregulated, and isoflavone and astaxanthin significantly downregulated Y2R mRNAs in HepG2. CGA and protocatechuic acid (PCA) (microbiota metabolite of anthocyanin) significantly upregulated mRNA levels in macrophages.
Isoflavone, astaxanthin, anthocyanin/PCA and CGA might prevent atherosclerosis from metabolic syndrome under chronic stress, combined with high-fat/high-sugar diet especially in subjects having Y2R gene promoter with SNPs able to transcribe in hepatocytes or macrophages.