Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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De novo Expression of Hepatic UCP3 Is Time-Dependently Related with Metabolic Function in Fenofibrate-Treated High Fat Diet Rats

고지방 섭취한 쥐에서 페노파이브레이트 복용에 의한 간 UCP3 발현 기간과 대사변화 관계

  • Park, Mi-Kyoung (Department of Internal Medicine, Medical Science Research Cente, Dong-A University College of Medicine) ;
  • Kang, Ah-Young (Department of Internal Medicine, Medical Science Research Center, Dong-A University College of Medicine) ;
  • Seo, Eun-Hui (Department of Pharmacology, Medical Science Research Center, Dong-A University College of Medicine) ;
  • Joe, Yeon-Soo (Department of Pharmacology, Medical Science Research Center, Dong-A University College of Medicine) ;
  • Kang, Soo-Jeong (Department of Pharmacology, Medical Science Research Center, Dong-A University College of Medicine) ;
  • Hong, Sook-Hee (Department of Pathology, Medical Science Research Center, Dong-A University College of Medicine) ;
  • Kim, Duk-Kyu (Department of Internal Medicine, 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)
  • 박미경 (동아대학교 의과대학 내과학교실, 동아대학교 의과학연구원) ;
  • 강아영 (동아대학교 의과대학 내과학교실, 동아대학교 의과학연구원) ;
  • 서은희 (동아대학교 의과대학 약리학교실, 동아대학교 의과학연구원) ;
  • 조연수 (동아대학교 의과대학 약리학교실, 동아대학교 의과학연구원) ;
  • 강수정 (동아대학교 의과대학 약리학교실, 동아대학교 의과학연구원) ;
  • 홍숙희 (동아대학교 의과대학 병리학교실, 동아대학교 의과학연구원) ;
  • 김덕규 (동아대학교 의과대학 내과학교실, 동아대학교 의과학연구원) ;
  • 이혜정 (동아대학교 의과대학 약리학교실, 동아대학교 의과학연구원)
  • Published : 2009.01.30
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Abstract

Uncoupling protein 3 (UCP3) is a mitochondrial protein that is expressed predominantly in skeletal muscle. It may play a role in altering metabolic function. However, its major physiological roles are not fully understood. Recently de novo expression of UCP3 in rat liver by fenofibrate was reported. We also reported previously that fenofibrate-induced de novo expression of UCP3 contributes to reduction of adipose tissue in obese rats. In the present study, we investigated that ienofibrate-induced expression of UCP3 in rat liver is related with metabolic function such as body weight and hepatic lipid content by time-dependent manner in high-fat diet rats. Eight-week-old male Sprague-Dawley rats were randomly divided into two groups; the high fat diet group (HF, n=16) and fenofibrate-treated high fat diet group (HFF, n=16). The mRNA expression of hepatic UCP3 was detected as early as 1 week of fenofibrate treatment by quantitative real-time PCR and the amount of mRNA was increased time-dependently. The mean body weight of the HFF group was significantly less com. pared with the HF group after 6 weeks of fenofibrate treatment, even though there was no difference of food intake between the two groups. Rectal temperature was increased during 4 to 6 weeks of fenofibrate treatment and body weight was decreased after 6 weeks of treatment. These results were corresponded with the increased amount of the expression of UCP3 mRNA and protein. We suggest that de novo expression of hepatic UCP3 is increased time-dependently with fenofibrate treatment and that the amount of expression is correlated with metabolic function.

Uncoupling protein 3 (UCP3)는 골격근에서 주로 발현되는 미토콘드리아 단백질이다. 생체의 대사기능에 관여할 것으로 알려져 있지만, 아직 그 역할에 대하여 깊이 연구되어 있지 않다. 최근에 고지혈증 치료제인 페노파이브레이트를 처치한 쥐의 간에서는 UCP3가 새로이 발현 유도된다는 것이 알려졌으며, 본 연구자들은 새로이 발현되는 UCP3가 비만쥐의 지방조직올 감소시키며, 인슐린 감수성을 증가시킨다는 보고를 하였다. 본 연구에서는 이러한 새로이 발현되는 UCP3의 시간에 따른 발현 양상과 대사 기능의 연관 관계를 규명하고자 하였다. 8주령 흰쥐를 두 군으로 나누어, 한 군은 고지방 식이를 실시하고(HF군), 다른 군은 고지방 식이와 페노파이브레이트(HFF군)를 함께 복용토록 하였다. 10주 동안 식이와 약물을 처리하면서, 1, 3, 6주에 간조직올 분석하였으며, 매주 먹이량, 체중, 체온을 측정하였다. 페노파이브레이트에 의하여 간에서 새로이 발현되는 UCP3는 2주부터 시작하여 3, 6주에 아주 높은 발현 양상을 보였다. 두 군 간의 먹이량의 차이는 없는 반면, 페노파이브레이트 처리군에서 6 주부터 시작하여 체중증가가 억제되며, 오히려 감소되는 경향을 보였다. 체온은 페노파이브레이트 처리군에서 6주부터 상승하기 시작하여, UCP3의 발현에 의한 간에서의 upcoupling 현상에 따른 발열현상으로 추측할 수 있다. 이상의 결과들로 유추해 볼 때, UCP3 발현이 3-6주부터 많은 양이 생성되어 생체의 대사 기능에 영향을 미치며, 이러한 시기와 연관되어 체중, 체온의 변화와 관련이 있는 것으로 생각한다.

Keywords

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