Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
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Medium-chain fatty acid enriched-diacylglycerol (MCE-DAG) accelerated cholesterol uptake and synthesis without impact on intracellular cholesterol level in HepG2

중쇄지방산 강화 디아실글리세롤(MCE-DAG)이 간세포 내 콜레스테롤 흡수 및 합성 기전에 미치는 영향

  • Received : 2019.05.14
  • Accepted : 2019.05.29
  • Published : 2019.06.30
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Abstract

The effects of medium-chain enriched diacylglycerol (MCE-DAG) oil on hepatic cholesterol homeostasis were investigated. HepG2 hepatocytes were treated with either 0.5, 1.0, or $1.5{\mu}g/mL$ of MCE-DAG for 48 h. There was no evidence of cytotoxicity by MCE-DAG up to $1.5{\mu}g/mL$. The level of proteins for cholesterol uptake including CLATHRIN and LDL receptor increased by MCE-DAG in a dose-dependent manner (p<0.05). Furthermore, proprotein convertase subtilisin/kexin type 9, an inhibitor of LDLR, was dose-dependently diminished (p<0.05), indicating cholesterol clearance raised. MCE-DAG significantly increased 3-hydroxy-3-methylglutaryl-coenzyme A reductase and acetyl-CoA acetyltransferase2 (p<0.05), required for cholesterol synthesis, and their transcriptional regulator sterol regulatory element-binding protein2 (p<0.05). These findings suggest that given conditions of prolonged sterol fasting in the current study activated both hepatic cholesterol synthesis and clearance by MCE-DAG. However, total intracellular level of cholesterol was not altered by MCE-DAG. Taken together, MCE-DAG has the potential to prevent hypercholesterolemia by increasing hepatic cholesterol uptake without affecting intracellular cholesterol level.

본 연구진은 선행연구에서 MCE-DAG를 섭취한 마우스에서 혈중 총 콜레스테롤과 LDL 콜레스테롤의 감소를 보고한 바 있어, 본 연구에서 in vitro를 통해 MCE-DAG와 간의 콜레스테롤 항상성 기전의 관련성을 구명하고자 하였다. LDLR과 같은 콜레스테롤 흡수 관련 인자의 발현이 MCE-DAG에 의해 증가한 반면, LDLR을 억제하는 PCSK9의 발현은 감소하였다. 또한, 콜레스테롤 합성 관련 인자인 HMGCR의 발현이 MCE-DAG에 의해 증가하였고, 전사조절인자인 SREBP2의 발현이 증가하였다. 이러한 결과들은 콜레스테롤의 합성과 흡수가 동시에 증가하였음을 뒷받침한다. 즉, 간 내 콜레스테롤 필요량이 증가함에 따라, 간의 콜레스테롤 합성 및 흡수를 활성화시켜 콜레스테롤 항상성을 유지하는 기전이 촉진되었음을 의미한다. 하지만 간 세포 내 총 콜레스테롤 양은 MCE-DAG에서 영향을 받지 않았다. 콜레스테롤 흡수 및 합성 기전이 촉진되었음에도 세포 내 콜레스테롤 농도가 증가하지 않은 현상은 담즙산 등 콜레스테롤 분비 촉진에 의한 것일 수 있다. 이러한 추론은 추후 콜레스테롤 분비 기전을 검증할 수 있는 실험을 설계하여 검증해볼 필요성이 있다. 결론적으로 MCE-DAG는 세포 내 콜레스테롤 흡수 작용을 촉진하는 효과가 있어 추후 기능성 유지로 활용 가능할 것으로 판단된다.

Keywords

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Fig. 1 Effects of MCE-DAG on hepatic cholesterol uptake in HepG2 cells. Data expressed as the mean±standard error.

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Fig. 2 Effects of MCE-DAG on hepatic cholesterol synthesis in hepatocytes.

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Fig. 3 Effects of MCE-DAG on the regulators for hepatic cholesterol homeostasis.

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Fig. 4 Intracellular total cholesterol contents on MCE-DAG.

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