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Effects of Sinetrol-XPur on Leptin-Deficient Obese Mice and Activation of cAMP-Dependent UCP-2

Leptin 유전자 결핍 동물모델을 이용한 시네트롤(Sinetrol-XPur)의 항비만 효과와 cAMP를 통한 UCP-2 활성화 기전 연구

  • 유재명 (경희대학교 동서의학대학원) ;
  • 이민희 (경희대학교 동서의학대학원) ;
  • 권한올 (경희대학교 동서의학대학원) ;
  • 최세규 ((주)알피코프) ;
  • 배문형 ((주)알피코프) ;
  • 김옥경 (전남대학교 식품영양과학부)
  • Received : 2015.12.21
  • Accepted : 2016.01.06
  • Published : 2016.04.30

Abstract

The present study investigated the effect of Sinetrol-XPur (polyphenolic Citrus spp. and Paullinia cupana Kunth dry extract) and defined the action mode for cyclic adenosine monophosphate (cAMP)-dependent uncoupling protein (UCP)-2 activation. Leptin-deficient obese mice were treated with two different doses, 100 mg/kg body weight (BW) and 300 mg/kg BW of each AIN93G supplement, for 7 weeks. Treatment of obese mice with both low and high doses of Sinetrol-XPur significantly reduced body weight gain compared to control obese mice. White adipose tissue weight of mice was reduced by 30.96% in high dose-supplemented groups. Serum total cholesterol and triglyceride were reduced by a high dose of Sinetrol-XPur by 20.02% and 30.96%, respectively. Serum level of high density lipoprotein (HDL) was significantly increased by treatment with both doses, as the ratio of HDL to low density lipoprotein increased by 138.78% and 171.49%, respectively. Regarding expression of biochemical factors related to lipid metabolism, fatty acid synthase significantly decreased and UCP-2 increased upon treatment with a high dose of Sinetrol-XPur, but there was no significant difference in lipoprotein lipase and hormone-sensitive lipase. To define cellular mechanism, intracellular cAMP levels in 3T3-L1 adipocytes significantly increased in a dose-dependent manner over the range of $50{\sim}250{\mu}m/mL$. The phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine clearly blocked cAMP, suggesting that Sinetrol-XPur promotes lipolysis of adipocytes through inhibition of cAMP-dependent PDE, resulting in induction of cAMP response element binding protein and UCP-2. These results suggest that Sinetrol-XPur supplementation is a viable option for reducing body weight and fat by improving serum lipid profiles and genetic expression of lipid metabolic factors, especially activation of cAMP-dependent UCP-2.

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