Ethanolic Extracts of Brassica campestris spp. rapa Roots Prevent High-Fat Diet-Induced Obesity via β3-Adrenergic Regulation of White Adipocyte Lipolytic Activity

다국어 초록 (Multilingual Abstract)

The influence of ethanolic extracts of Brassica campestris spp. rapa roots (EBR) on obesity was examined in imprinting control region (ICR) mice fed a high-fat diet (HFD) and in 3T3-L1 adipocytes. The ICR mice used were divided into regular diet, HFD, EBR (50mg/kg/day EBR administered orally), and orlistat (10mg/kg/day orlistat administered orally) groups. The molecular mechanism of the anti-obesity effect of EBR was investigated in 3T3-L1 adipocytes as well as in HFD-fed ICR mice. In the obese mouse model, both weight gain and epididymal fat accumulation were highly suppressed by the daily oral administration of 50mg/kg EBR for 8 weeks, whereas the overall amount of food intake was not affected. EBR treatment induced the expression in white adipocytes of lipolysis-related genes, including β3-adrenergic receptor (β3-AR), hormone-sensitive lipase (HSL), adipose triglyceride lipase, and uncoupling protein 2. Furthermore, the activation of cyclic AMP-dependent protein kinase, HSL, and extracellular signal-regulated kinase was induced in EBR-treated 3T3-L1 cells. The lipolytic effect of EBR involved β3-AR modulation, as inferred from the inhibition by the β3-AR antagonist propranolol. These results suggest that EBR may have potential as a safe and effective anti-obesity agent via the inhibition of adipocyte lipid accumulation and the stimulation of β3-AR-dependent lipolysis.

참고문헌 (Reference)

1 방면호, "식용식물자원으로부터 활성물질의 탐색-XX.순무(Brassica campestris ssp rapa)뿌리로부터 지질화합물의 분리" 한국응용생명화학회 50 (50): 233-237, 2007

2 방면호, "식용식물자원으로부터 활성물질의 탐색 XXII.순무(Brassica campestris ssp rapa) 뿌리로부터 인돌 화합물의분리 및 hACAT 저해 활성" 한국응용생명화학회 51 (51): 65-69, 2008

3 최연희, "순무(Brassica campestris ssp rapa) 뿌리의 화학성분" 한국생약학회 35 (35): 259-263, 2004

4 Tontonoz P., "mPPAR gamma 2: tissuespecific regulator of an adipocyte enhancer" 8 : 1224-1234, 1994

5 Fleury C., "Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia" 15 : 269-272, 1997

6 Clifford GM, "Translocation of hormone-sensitive lipase and perilipin upon lipolytic stimulation of rat adipocytes" 275 : 5011-5015, 2000

7 Erlanson-Albertsson C., "The role of uncoupling proteins in the regulation of metabolism" 178 : 405-412, 2003

8 Brasaemle DL, "The lipolytic stimulation of 3T3-L1 adipocytes promotes the translocation of hormone-sensitive lipase to the surfaces of lipid storage droplets" 1483 : 251-262, 2000

9 Greenberg AS, "Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signalregulated kinase pathway" 276 : 45456-45461, 2001

10 Greenberg AS, "Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signalregulated kinase pathway" 276 : 45456-45461, 2001

11 Carmen GY, "Signalling mechanisms regulating lipolysis" 18 : 401-408, 2006

12 Cho KJ, "Signaling pathways implicated in alpha-melanocyte stimulating hormone-induced lipolysis in 3T3-L1 adipocytes" 96 : 869-878, 2005

13 Zhang Y., "Regulation of adiponectin and leptin gene expression in white and brown adipose tissues: influence of beta3-adrenergic agonists, retinoic acid, leptin and fasting" 1584 : 115-122, 2002

14 Watt MJ, "Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue" 290 : E500-E508, 2006

15 Luo S., "Quantitation of protein on gels and blots by infrared fluorescence of Coomassie blue and Fast Green" 350 : 233-238, 2006

16 Kim YH, "Protective effect of the ethanol extract of the roots of Brassica rapa on cisplatin-induced nephrotoxicity in LLC-PK1 cells and rats" 29 : 2436-2441, 2006

17 Festuccia WT, "PPARgamma agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control" 49 : 2427-2436, 2006

18 Kopelman PG, "Obesity as a medical problem" 404 : 635-643, 2000

19 Holm C., "Molecular mechanisms regulating hormone-sensitive lipase and lipolysis" 20 : 365-393, 2000

20 Holm C., "Molecular mechanisms regulating hormone-sensitive lipase and lipolysis" 31 : 1120-1124, 2003

21 Burns KA, "Modulation of PPAR activity via phosphorylation" 1771 : 952-960, 2007

22 Egan JJ, "Mechanism of hormone-stimulated lipolysis in adipocytes: translocation of hormone-sensitive lipase to the lipid storage droplet" 89 : 8537-8541, 1992

23 Pang J., "Ilex paraguariensis extract ameliorates obesity induced by high-fat diet: potential role of AMPK in the visceral adipose tissue" 276 : 178-185, 2008

24 Yajima H., "Identification of peroxisome-proliferator responsive element in the mouse HSL gene" 352 : 526-531, 2007

25 Fredrikson G., "Hormonesensitive lipase of rat adipose tissue. Purification and some properties" 256 : 6311-6320, 1981

26 Stra°lfors P., "Hormonal regulation of hormone-sensitive lipase in intact adipocytes: identification of phosphorylated sites and effects on the phosphorylation by lipolytic hormones and insulin" 81 : 3317-3321, 1984

27 Chapman MJ, "Fibrates in 2003: therapeutic action in atherogenic dyslipidaemia and future perspectives" 171 : 1-13, 2003

28 Jung UJ, "Effects of the ethanol extract of the roots of Brassica rapa on glucose and lipid metabolism in C57BL=KsJ-db=db mice" 27 : 158-167, 2008

29 Khovidhunkit W., "Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host" 45 : 1169-1196, 2004

30 Padwal RS, "Drug treatments for obesity: orlistat, sibutramine, and rimonabant" 369 : 71-77, 2007

31 Bray GA, "Drug treatment of obesity" 2 : 403-418, 2001

32 Lafontaine JA, "Discovery of potent and orally bioavailable heterocycle-based beta3-adrenergic receptor agonists, potential therapeutics for the treatment of obesity" 17 : 5245-5250, 2007

33 Large V., "Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects" 40 : 2059-2066, 1999

34 Wolfe K., "Antioxidant activity of apple peels" 51 : 609-614, 2003

35 Kang M., "Anti-obesity effect of PM-F2- OB, an anti-obesity herbal formulation, on rats fed a high-fat diet" 27 : 1251-1256, 2004

36 Dey L., "Anti-diabetic and anti-obese effects of ginseng berry extract: comparison between intraperitoneal and oral administrations" 30 : 645-647, 2002

37 Ahima RS, "Adipose tissue as an endocrine organ" 14 (14): 242S-249S, 2006

38 Londos C., "ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells" 10 : 51-58, 1999