title: Rubi Fructus (Rubus coreanus) activates the expression of thermogenic genes in vivo and in vitro.
abstract: OBJECTIVE
  To investigate the anti-obesity effect of Rubi Fructus (RF) extract using brown adipose tissue (BAT) and primary brown preadipocytes in vivo and in vitro.
  
  
  METHODS
  Male C57BL/6 J mice (n=5 per group) were fed a high-fat diet (HFD) for 10 weeks with or without RF. Brown preadipocytes from the interscapular BAT of mice (age, post-natal days 1-3) were cultured with differentiation media (DM) including isobutylmethylxanthine, dexamethasone, T3, indomethacin and insulin with or without RF.
  
  
  RESULTS
  In HFD-induced obese C57BL/6 J mice, long-term RF treatment significantly reduced weight gain as well as the weights of the white adipose tissue, liver and spleen. Serum levels of total cholesterol and low-density lipoprotein cholesterol were also reduced in the HFD group which received RF treatment. Furthermore, RF induced thermogenic-, adipogenic- and mitochondria-related gene expressions in BAT. In primary brown adipocytes, RF effectively stimulated the expressions of thermogenic- and mitochondria-related genes. In addition, to examine whether LIPIN1, a regulator of adipocyte differentiation, is regulated by RF, Lipin1 small interfering RNA (siRNA) and RF were pretreated in primary brown adipocytes. Pretreatment with Lipin1 siRNA and RF downregulated the DM-induced expression levels of thermogenic- and mitochondria-related genes. Moreover, RF markedly upregulated AMP-activated protein kinase. Our study shows that RF is capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes.
  
  
  CONCLUSIONS
  This study demonstrates that RF prevents the development of obesity in mice fed with a HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes, which suggests that RF has potential as a therapeutic application for the treatment or prevention of obesity.
authors.affiliation: 1] Center for Metabolic Function Regulation, Wonkwang University, Iksan, Korea [2] College of Korean Medicine, Institute of Korean Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: M Y
authors.initials: MY
authors.lastname: Jeong
authors.affiliation: College of Korean Medicine, Institute of Korean Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: H L
authors.initials: HL
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Institute of Korean Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.affiliation: College of Korean Medicine, Institute of Korean Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Jung
authors.affiliation: College of Korean Medicine, Institute of Korean Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: D H
authors.initials: DH
authors.lastname: Youn
authors.affiliation: College of Pharmacy, Dongduk Women's University, Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Oriental Medicine Resources, College of Environmental & Bioresources Sciences, Chonbuk National University, Iksan, Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Jin
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University, Iksan, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: So
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University, Iksan, Korea.
authors.forename: R
authors.initials: R
authors.lastname: Park
authors.affiliation: College of Korean Medicine, Institute of Korean Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Cosmeceutical Science, Daegu Hanny University, Gyeongsan, Korea.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University, Iksan, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Hong
authors.affiliation: College of Korean Medicine, Institute of Korean Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Um
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000473:pathology*; D028321:Plant Preparations / Q000494:pharmacology*; D065856:Rubus; D022722:Thermogenesis / Q000187:drug effects / Q000235:genetics*
chemical_list: D028321:Plant Preparations
references.citation: J Endocrinol. 2002 Oct;175(1):185-91
references.pmid: 12379502
references.citation: Lancet. 2005 Apr 9-15;365(9467):1333-46
references.pmid: 15823385
references.citation: EMBO Rep. 2005 Dec;6(12):1137-42
references.pmid: 16319959
references.citation: Nat Genet. 2001 Jan;27(1):121-4
references.pmid: 11138012
references.citation: Prostaglandins Leukot Essent Fatty Acids. 1995 Feb-Mar;52(2-3):121-7
references.pmid: 7784447
references.citation: Biol Pharm Bull. 2003 Oct;26(10):1436-41
references.pmid: 14519951
references.citation: Endocr Rev. 2005 May;26(3):439-51
references.pmid: 15897298
references.citation: PLoS One. 2012;7(6):e39165
references.pmid: 22720061
references.citation: Exp Biol Med (Maywood). 2001 Dec;226(11):982-90
references.pmid: 11743133
references.citation: Biochem Biophys Res Commun. 2008 Sep 26;374(3):587-91
references.pmid: 18656451
references.citation: J Lipid Res. 2007 Jan;48(1):201-6
references.pmid: 17035674
references.citation: Cell Metab. 2005 Jan;1(1):73-83
references.pmid: 16054046
references.citation: Int J Biochem Cell Biol. 2004 Nov;36(11):2098-104
references.pmid: 15313455
references.citation: Nature. 2000 Apr 6;404(6778):635-43
references.pmid: 10766250
references.citation: Obes Res. 2003 Oct;11(10):1182-91
references.pmid: 14569043
references.citation: Nutr Res Pract. 2011 Oct;5(5):429-34
references.pmid: 22125680
references.citation: FASEB J. 2009 Sep;23(9):3113-20
references.pmid: 19417078
references.citation: Trends Pharmacol Sci. 2009 Aug;30(8):387-96
references.pmid: 19595466
references.citation: J Biol Chem. 2005 Sep 23;280(38):32883-9
references.pmid: 16049017
references.citation: Diabetes. 2007 Sep;56(9):2395-9
references.pmid: 17563064
references.citation: Nature. 2008 Aug 21;454(7207):1000-4
references.pmid: 18719589
references.citation: Nature. 2009 Aug 27;460(7259):1154-8
references.pmid: 19641492
references.citation: Biochim Biophys Acta. 2001 Mar 1;1504(1):82-106
references.pmid: 11239487
references.citation: Evid Based Complement Alternat Med. 2013;2013:475386
references.pmid: 24288561
references.citation: Mol Cell Biol. 2004 Mar;24(5):1918-29
references.pmid: 14966273
references.citation: Endocrinology. 2010 Mar;151(3):980-92
references.pmid: 20133456
references.citation: Gene. 2002 Mar 6;286(1):81-9
references.pmid: 11943463
references.citation: J Biol Chem. 2005 Apr 8;280(14):13560-7
references.pmid: 15653680
references.citation: N Engl J Med. 2009 Apr 9;360(15):1500-8
references.pmid: 19357405
references.citation: Mol Cell Biol. 2012 Dec;32(23):4794-810
references.pmid: 23028044
references.citation: Histochemistry. 1992 Jul;97(6):493-7
references.pmid: 1385366
references.citation: J Biol Chem. 1999 Dec 3;274(49):34795-802
references.pmid: 10574950
references.citation: Mol Cell Endocrinol. 2013 Feb 25;366(2):194-203
references.pmid: 22750051
references.citation: Diabetes. 2006 Oct;55(10):2811-8
references.pmid: 17003347
references.citation: N Engl J Med. 2009 Apr 9;360(15):1509-17
references.pmid: 19357406
references.citation: J Agric Food Chem. 2012 May 23;60(20):5121-7
references.pmid: 22563950
references.citation: Hum Mol Genet. 2006 Feb 1;15(3):377-86
references.pmid: 16357106
references.citation: FEBS Lett. 2002 Dec 18;532(3):345-50
references.pmid: 12482590
references.citation: J Clin Invest. 2003 Jan;111(2):225-30
references.pmid: 12531878
references.citation: Nature. 2001 Jan 18;409(6818):307-12
references.pmid: 11201732
references.citation: N Engl J Med. 2009 Apr 9;360(15):1518-25
references.pmid: 19357407