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Effects of Sinetrol-XPur on Leptin-Deficient Obese Mice and Activation of cAMP-Dependent UCP-2
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 Title & Authors
Effects of Sinetrol-XPur on Leptin-Deficient Obese Mice and Activation of cAMP-Dependent UCP-2
Yoo, Jae Myeong; Lee, Minhee; Kwon, Han Ol; Choi, Sei Gyu; Bae, Mun Hyoung; Kim, Ok-Kyung;
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 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 . 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.
 Keywords
anti-obesity;Sinetrol-XPur;citrus;ob/ob mice;
 Language
Korean
 Cited by
 References
1.
Ingalls AM, Dickie MM, Snell GD. 1996. Obese, a new mutation in the house mouse. Obes Res 4: 101. crossref(new window)

2.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. 1994. Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425-432. crossref(new window)

3.
Inui A. 2001. Ghrelin: an orexigenic and somatotrophic signal from the stomach. Nat Rev Neurosci 2: 551-560. crossref(new window)

4.
Xiong Y, Qu Z, Chen N, Gong H, Song M, Chen X, Du J, Xu C. 2014. The local corticotropin-releasing hormone receptor 2 signalling pathway partly mediates hypoxia-induced increases in lipolysis via the cAMP-protein kinase A signalling pathway in white adipose tissue. Mol Cell Endocrinol 392: 106-114. crossref(new window)

5.
Aubert J, Champigny O, Saint-Marc P, Negrel R, Collins S, Ricquier D, Ailhaud G. 1997. Up-regulation of UCP-2 gene expression by PPAR agonists in preadipose and adipose cells. Biochem Biophys Res Commun 238: 606-611. crossref(new window)

6.
Cho YS, Jang EM, Jang SM, Chun MS, Shon MY, Kim MJ, Lee MK. 2007. Effect of grape seed water extract on lipid metabolism and erythrocyte antioxidant defense system in high-fat diet-induced obese C57BL/6 mice. J Korean Soc Food Sci Nutr 36: 1537-1543. crossref(new window)

7.
Chen D, Daniel KG, Kuhn DJ, Kazi A, Bhuiyan M, Li L, Wang Z, Wan SB, Lam WH, Chan TH, Dou QP. 2004. Green tea and tea polyphenols in cancer prevention. Front Biosci 9: 2618-2631. crossref(new window)

8.
Frankel EN, Kanner J, German JB, Parks E, Kinsella JE. 1993. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 341: 454-457. crossref(new window)

9.
Kuppusamy UR, Das NP. 1992. Effects of flavonoids on cyclic AMP phosphodiesterase and lipid mobilization in rat adipocytes. Biochem Pharmacol 44: 1307-1315. crossref(new window)

10.
Kopelman PG. 2000. Obesity as a medical problem. Nature 404: 635-643.

11.
Dallas C, Gerbi A, Elbez Y, Caillard P, Zamaria N, Cloarec M. 2014. Clinical study to assess the efficacy and safety of a citrus polyphenolic extract of red orange, grapefruit, and orange (Sinetrol-XPur) on weight management and metabolic parameters in healthy overweight individuals. Phytother Res 28: 212-218. crossref(new window)

12.
Dallas C, Gerbi A, Tenca G, Juchaux F, Bernard FX. 2008. Lipolytic effect of a polyphenolic citrus dry extract of red orange, grapefruit, orange (SINETROL) in human body fat adipocytes. Mechanism of action by inhibition of cAMPphosphodiesterase (PDE). Phytomedicine 15: 783-792. crossref(new window)

13.
Chae MH, No JG, Jhon DY. 2007. Hangbisan sulfur-based oriental medicine, lowers the blood cholesterol level of ob/ ob obese mice. J Korean Soc Food Sci Nutr 36: 27-31. crossref(new window)

14.
Chua S, Leibel RL. 1997. Obesity genes: Molecular and metabolic mechanism. Diabetes Rev 5: 2-7.

15.
Visscher TL, Seidell JC. 2001. The public health impact of obesity. Annu Rev Public Health 22: 355-375. crossref(new window)

16.
Kim AR, Hwang YG, Lee JJ, Jung HO, Lee MY. 2011. Effects of Eriobotrya japonica Lindl. (loquat) leaf ethanol extract on cholesterol and antioxidative activity in rats fed a high-fat/high-cholesterol diet. J Korean Soc Food Sci Nutr 40: 673-681. crossref(new window)

17.
Park PJ, Kim CW, Cho SY, Pha CS, Seo DB, Lee SJ. 2010. Aqueous spray-dried green tea extract regulates body weight and epididymal fat accumulation in mice. Korean J Food Sci Technol 42: 103-108.

18.
Lee JS, Lee MK, Ha TY, Bok SH, Park HM, Jeong KS, Woo MN, Do GM, Yeo JY, Choi MS. 2006. Supplementation of whole persimmon leaf improves lipid profiles and suppresses body weight gain in rats fed high-fat diet. Food Chem Toxicol 44: 1875-1883. crossref(new window)

19.
Imano H, Noda H, Kitamura A, Sato S, Kiyama M, Sankai T, Ohira T, Nakamura M, Yamagishi K, Ikeda A, Shimamoto T, Iso H. 2011. Low-density lipoprotein cholesterol and risk of coronary heart disease among Japanese men and women: The Circulatory Risk in Communities Study (CIRCS). Prev Med 52: 381-386. crossref(new window)

20.
Cook NC, Samman S. 1996. Flavonoids-Chemistry, metabolism, cardioprotective effects, and dietary sources. J Nutr Biochem 7: 66-76. crossref(new window)

21.
Kim HK, Jeong TS, Lee MK, Park YB, Choi MS. 2003. Lipid-lowering efficacy of hesperetin metabolites in highcholesterol fed rats. Clin Chim Acta 327: 129-137. crossref(new window)

22.
Ronnett GV, Kim EK, Landree LE, Tu Y. 2005. Fatty acid metabolism as a target for obesity treatment. Physiol Behav 85: 25-35. crossref(new window)

23.
Auwerx J, Leroy P, Schoonjans K. 1992. Lipoprotein lipase: recent contributions from molecular biology. Crit Rev Clin Lab Sci 29: 243-268. crossref(new window)

24.
Lee JJ, Chung CS, Kim JG, Choi BD. 2000. Effects of fasting- refeeding on rat adipose tissue lipoprotein lipase activity and lipogenesis: influence of food restriction during refeeding. J Korean Soc Food Sci Nutr 29: 471-748.

25.
Langin D, Holm C, Lafontan M. 1996. Adipocyte hormonesensitive lipase: a major regulator of lipid metabolism. Proc Nutr Soc 55: 93-109. crossref(new window)

26.
Steinberg D, Khoo JC. 1977. Hormone-sensitive lipase of adipose tissue. Fed Proc 36: 1986-1990.

27.
Conti AC, Blendy JA. 2004. Regulation of antidepressant activity by cAMP response element binding proteins. Mol Neurobiol 30: 143-155. crossref(new window)

28.
Johannessen M, Delghandi MP, Moens U. 2004. What turns CREB on?. Cell Signal 16: 1211-1227. crossref(new window)

29.
Puigserver P, Herron D, Gianotti M, Palou A, Cannon B, Nedergaard J. 1992. Induction and degradation of the uncoupling protein thermogenin in brown adipocytes in vitro and in vivo. Evidence for a rapidly degradable pool. Biochem J 284: 393-398. crossref(new window)

30.
Vidal-Puig A, Solanes G, Grujic D, Flier JS, Lowell BB. 1997. UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue. Biochem Biophys Res Commun 235: 79-82. crossref(new window)

31.
Gong DW, He Y, Karas M, Reitman M. 1997. Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, ${\beta}3-adrenergic agonists, and leptin. J Biol Chem 272: 24129-21432. crossref(new window)

32.
Yanovski JA, Diament AL, Sovik KN, Nguyen TT, Li H, Sebring NG, Warden CH. 2000. Associations between uncoupling protein 2, body composition, and resting energy expenditure in lean and obese African American, Caucasian, and Asian children. Am J Clin Nutr 71: 1405-1420.