Search for nutrients and drugs to improve dyslipidemia by monitoring Y2 receptor gene expression

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K00860
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: Kobe Women's University (2018); University of Hyogo (2016-2017)
• Principal Investigator: KAJI Hidesuke 神戸女子大学, 看護学部, 教授 (90224401)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ニューロペプチドY / Y2受容体 / 栄養素 / HepG2 / マクロファージ / mRNA / ABCG1 / SNP

Outline of Final Research Achievements

Stress and high caloric diet caused metabolic syndrome by neuropeptide Y (NPY) through NPY receptor 2 (Y2R). We have previously reported the relation between serum HDL-cholesterol levels and single nucleotide polymorphism (SNP)s on the regulatory region of Y2R gene as well as its causal mechanism. Human hepatom cells HepG2 and human THP-1 derived macrophages had heterozygous gene promoter SNP type that is specifically transcribed in each cell. We examined the effect of anti-atherogenic nutrients and drugs on mRNA levels of Y2R and cholesterol efflux-related molecules, ABCA1 and ABCG1 in cultured HepG2 and macrophages by using real time PCR methods. Isoflavone and astaxanthin significantly decreased Y2R mRNA levels in HepG2. Protocatechuic acids significantly increased ABCG1 and Y2R mRNA levels in macrophages. These results suggest that isoflavone, astaxanthin and protocatechuic acids might prevent atherosclerosis in part through NPY-Y2R mechanism.

Free Research Field

内分泌代謝内科学

Academic Significance and Societal Importance of the Research Achievements

個々の遺伝子多型に基づく精密医療は癌ゲノム医療で進んでいるが、動脈硬化の病態に基づく予防・治療においても今後の応用が期待される。本研究ではストレスと高糖脂食が重なって起こるメタボリック症候群へのNPY-Y2Rの関与がSNPタイプによって異なり、それに応じた栄養素や薬剤の選択を考えていく契機となる成果と考えている。今後の臨床応用には動脈硬化指標をアウトカムとするSNPタイプに応じた栄養素の有用性の検証が必要である。