Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Alteration of Lipid Metabolism Related Proteins in Liver of High-Fat Fed Obese Mice

고지방식이 비만쥐의 지방관련 단백질의 변화

  • Seo, Eun-Hui (Department of Pharmacology, Medical Science Research Center, Dong-A University College of Medicine) ;
  • Han, Ying (Department of Pharmacology, Medical Science Research Center, Dong-A University College of Medicine) ;
  • Park, So-Young (Department of Pharmacology, Medical Science Research Center, Dong-A University College of Medicine) ;
  • Koh, Hyong-Jong (Department of Pharmacology, Medical Science Research Center, Dong-A University College of Medicine) ;
  • Lee, Hye-Jeong (Department of Pharmacology, Medical Science Research Center, Dong-A University College of Medicine)
  • 서은희 (동아대학교 의과대학 약리학교실) ;
  • 한영 (동아대학교 의과대학 약리학교실) ;
  • 박소영 (동아대학교 의과대학 약리학교실) ;
  • 고형종 (동아대학교 의과대학 약리학교실) ;
  • 이혜정 (동아대학교 의과대학 약리학교실)
  • Received : 2010.05.13
  • Accepted : 2010.05.24
  • Published : 2010.07.30
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Abstract

Obesity and being overweight are strongly associated with the development of metabolic disease such as diabetes, hypertension, dyslipidemia. High-fat diet (HFD) is one of the most important factors which cause obesity. In this study, C57BL/6 mice were treated with a HFD for 22 weeks in order to induce obesity and hyperglycemia. Twenty-two weeks later, body weight and plasma glucose level of the HFD group were significantly increased, compared with the normal diet (ND) group. Intra-peritoneal glucose tolerance test (IPGTT) showed glucose intolerance in the HFD group compared with the ND group. These results confirmed that a HFD induced obesity and hyperglycemia in C57BL/6 mice. Plasma levels of triglyceride (TG) and total cholesterol (TC) were increased in the HFD group compared with the ND group. Hepatic levels of TG and TC were also increased by a HFD. To investigate the alteration of lipid metabolism in liver, proteins which are related to lipid metabolism were observed. Among lipid synthesis related enzymes, fatty acid synthase (FAS) and glycerol phosphate acyl transferase (GPAT) were significantly increased in the HFD group. Apolipoprotein B (apoB) and microsomal triglyceride transport protein (MTP), which are related to lipid transport, were significantly increased in the HFD group. Interestingly, protein level and phosphorylation of AMP-activated protein kinase (AMPK), which is known as a metabolic regulator, were significantly increased in the HFD group compared with the ND group. In the present study we suggest that HFD may physiologically increase the proteins which are related with lipid synthesis and lipid transport, but that HFD may paradoxically induce the activation of AMPK.

과체중과 비만은 당뇨병, 고혈압, 고지혈증과 같은 신진 대사 질환의 발병과 강력하게 연관되어 있다. 비만의 원인은 여러가지가 있겠지만, 고지방식이는 비만의 원인 중 가장 중요한 요소 중 하나이다. 본 연구에서는 C57BL/6 생쥐에게 22주간의 고지방 식이를 주었으며, 이를 통해 비만과 고혈당을 유도하였다. 22주 후에 고지방식이를 한 생쥐들에서 체중과 혈장 포도당 수준이 정상 식이를 한 생쥐들에 비해 크게 증가함을 관찰하였다. 복막 내 당 부하 검사(IPGTT)에서도 고지방 식이를 한 생쥐들은 정상 식이를 한 생쥐들에 비해서 당 내성 이상 반응을 보여주었다. 이러한 결과들은 고지방식이가 C57BL/6 생쥐에서 비만 및 고혈당을 유도한다는 사실을 확인시켜 주었다. 고지방식이군 생쥐들에서는 정상식이군의 생쥐들에 비해 혈장의 중성지방과 총 콜레스테롤의 양이 증가됨이 관찰되었다. 간에서의 중성지방 및 총 콜레스테롤의 수준도 역시 증가하였다. 따라서, 간에서의 지질대사가 어떻게 변하였는지를 알기 위해, 지질대사에 관련된 단백질들의 변화를 관찰하였다. 지방 합성과 관련된 효소들 중 FAS와 GPAT가 고지방식이 군에서 의미있게 증가 되어있었으며, 지방 수송에 관련하는 단백질 중에서도 ApoB 및 MTP의 큰 증가가 고지방식이군에서 관찰되었다. 흥미롭게도, 대사 조절 인자로 알려진 AMPK의 단백질의 양과 인산화 정도는 정상식이군에 비해 고지방식이군에서 의미있게 증가되었음이 관찰되었다. 결론적으로, 본 연구에서 우리는 고지방식이가 지질 합성과 지질 수송과정을 생리학적으로 증가시키지만, 역설적으로 AMPK의 활성화를 유발한다는 것을 확인하였다.

Keywords

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