1α, 25-dihydroxy Vitamin D3 containing fractions of Catharanthus roseus leaf aqueous extract inhibit preadipocyte differentiation and induce lipolysis in 3T3-L1 cells.
3T3-L1
Adipogenesis
Catharanthus roseus
Lipolysis
Obesity
Vitamin D3
Journal
BMC complementary and alternative medicine
ISSN: 1472-6882
Titre abrégé: BMC Complement Altern Med
Pays: England
ID NLM: 101088661
Informations de publication
Date de publication:
29 Nov 2019
29 Nov 2019
Historique:
received:
16
05
2019
accepted:
14
11
2019
entrez:
1
12
2019
pubmed:
1
12
2019
medline:
22
1
2020
Statut:
epublish
Résumé
To investigate the potential of Catharanthus roseus leaf aqueous crude extract (CRACE) as a regulator of adipocyte development and function. 3T3-L1 adipogenesis model was used to investigate the effect of CRACE on adipogenesis. 3T3-L1 preadipocytes (for adipogenic differentiation) and mature 3T3-L1 adipocytes (for adipocyte function) were treated with non-toxic doses of CRACE. The outcomes were corroborated by intracellular lipid accumulation, expression of pro-and anti-adipogenic effector molecules. To investigate CRACE mediated lipolysis, cAMP accumulation, glycerol release and phosphorylation of key effector molecules were tested in treated mature adipocytes. Finally, the extract was fractionated to identify the active molecule/s in the extract. CRACE significantly reduced adipocyte differentiation by modulating PPARγ expression. At early stage CRACE directly targeted Lipin1 expression and consequently impacted KLF7, subsequently expression of GATA2, CEBPα, SREBP1c were targeted, with PPARγ expression, particularly curtailed. While CRACE significantly reduced several lipogenic genes like FAS and GPD1 in mature adipocytes, concomitantly, it greatly increased lipolysis resulting in decreased lipid accumulation in mature adipocytes. The increase in lipolysis was due to decreased Akt activation, increased cAMP level, and PKA activity. The fractionation of CRACE allowed identification of two fractions with potent anti-adipogenic activity. Both the fractions contained 1α, 25-dihydroxy Vitamin D3 as major component. 1α, 25-dihydroxy Vitamin D3 containing CRACE can be developed into an effective anti-obesity formulation that decreases adipogenesis and increases lipid catabolism.
Sections du résumé
BACKGROUND
BACKGROUND
To investigate the potential of Catharanthus roseus leaf aqueous crude extract (CRACE) as a regulator of adipocyte development and function.
METHODS
METHODS
3T3-L1 adipogenesis model was used to investigate the effect of CRACE on adipogenesis. 3T3-L1 preadipocytes (for adipogenic differentiation) and mature 3T3-L1 adipocytes (for adipocyte function) were treated with non-toxic doses of CRACE. The outcomes were corroborated by intracellular lipid accumulation, expression of pro-and anti-adipogenic effector molecules. To investigate CRACE mediated lipolysis, cAMP accumulation, glycerol release and phosphorylation of key effector molecules were tested in treated mature adipocytes. Finally, the extract was fractionated to identify the active molecule/s in the extract.
RESULTS
RESULTS
CRACE significantly reduced adipocyte differentiation by modulating PPARγ expression. At early stage CRACE directly targeted Lipin1 expression and consequently impacted KLF7, subsequently expression of GATA2, CEBPα, SREBP1c were targeted, with PPARγ expression, particularly curtailed. While CRACE significantly reduced several lipogenic genes like FAS and GPD1 in mature adipocytes, concomitantly, it greatly increased lipolysis resulting in decreased lipid accumulation in mature adipocytes. The increase in lipolysis was due to decreased Akt activation, increased cAMP level, and PKA activity. The fractionation of CRACE allowed identification of two fractions with potent anti-adipogenic activity. Both the fractions contained 1α, 25-dihydroxy Vitamin D3 as major component.
CONCLUSIONS
CONCLUSIONS
1α, 25-dihydroxy Vitamin D3 containing CRACE can be developed into an effective anti-obesity formulation that decreases adipogenesis and increases lipid catabolism.
Identifiants
pubmed: 31783835
doi: 10.1186/s12906-019-2754-7
pii: 10.1186/s12906-019-2754-7
pmc: PMC6883588
doi:
Substances chimiques
Plant Extracts
0
Calcitriol
FXC9231JVH
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
338Références
Cold Spring Harb Perspect Biol. 2012 Sep 01;4(9):a008417
pubmed: 22952395
Arch Biochem Biophys. 2017 Feb 1;615:22-34
pubmed: 28063949
J Gen Virol. 2008 May;89(Pt 5):1225-1230
pubmed: 18420801
IUBMB Life. 2004 Oct;56(10):595-600
pubmed: 15814457
J Mol Endocrinol. 2014 Jun;52(3):R199-222
pubmed: 24577718
J Biol Chem. 1985 Dec 5;260(28):15122-9
pubmed: 2415513
J Biol Chem. 2008 Dec 12;283(50):34896-906
pubmed: 18930917
Nutrition. 2016 Jun;32(6):702-8
pubmed: 26899162
Cell Metab. 2012 Aug 8;16(2):189-201
pubmed: 22863804
Nat Protoc. 2013 Jun;8(6):1149-54
pubmed: 23702831
J Biol Chem. 1998 Nov 13;273(46):30057-60
pubmed: 9804754
BMC Complement Altern Med. 2003 Sep 2;3:4
pubmed: 12950994
Biochem J. 2003 Nov 1;375(Pt 3):539-49
pubmed: 18320708
J Ethnopharmacol. 2008 Sep 2;119(1):81-6
pubmed: 18588966
Cell Physiol Biochem. 2018;48(1):397-408
pubmed: 30016791
Cell Metab. 2006 Oct;4(4):263-73
pubmed: 17011499
PLoS One. 2012;7(1):e30831
pubmed: 22292054
Biochem Biophys Res Commun. 2000 Aug 11;274(3):631-4
pubmed: 10924329
Asian Pac J Trop Biomed. 2012 May;2(5):411-20
pubmed: 23569941
Dev Biol. 2013 Jan 15;373(2):235-43
pubmed: 23142072
Biochem J. 2006 Oct 1;399(1):131-9
pubmed: 16787385
Acta Pol Pharm. 2011 Nov-Dec;68(6):927-35
pubmed: 22125959
Clin Chem. 2018 Jan;64(1):24-29
pubmed: 29295834
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Apr;1864(4):596-607
pubmed: 30597201
J Ethnopharmacol. 1980 Mar;2(1):49-55
pubmed: 7464183
West Indian Med J. 1982 Dec;31(4):194-7
pubmed: 7157790
Nat Rev Mol Cell Biol. 2011 Sep 28;12(11):722-34
pubmed: 21952300
Nat Med. 2012 Aug;18(8):1279-85
pubmed: 22842477
J Biol Chem. 2006 Apr 21;281(16):11205-13
pubmed: 16467308
J Clin Invest. 2003 Dec;112(12):1821-30
pubmed: 14679177
Diabetes. 1997 Aug;46(8):1319-27
pubmed: 9231657
Am J Physiol Endocrinol Metab. 2006 May;290(5):E916-24
pubmed: 16368784
PLoS Genet. 2007 Apr 27;3(4):e64
pubmed: 17465682
Physiol Rev. 1998 Jul;78(3):783-809
pubmed: 9674695
PLoS One. 2012;7(12):e52171
pubmed: 23272223
Cell Metab. 2010 Mar 3;11(3):194-205
pubmed: 20197052
Biochim Biophys Acta. 1995 Oct 19;1269(1):91-7
pubmed: 7578277
J Biol Chem. 2002 Mar 29;277(13):11019-25
pubmed: 11790787
Cell. 1994 Dec 30;79(7):1147-56
pubmed: 8001151
Endocrinology. 1994 May;134(5):2221-9
pubmed: 8156925
Biochem J. 2009 Dec 14;425(1):215-23
pubmed: 19811452
J Lipid Res. 2012 Nov;53(11):2296-306
pubmed: 22941773
IUBMB Life. 2004 Jul;56(7):379-85
pubmed: 15545214
Biochem J. 2013 Jul 1;453(1):49-60
pubmed: 23627357
Ann N Y Acad Sci. 1999 Nov 18;892:155-68
pubmed: 10842661
Exp Mol Med. 2011 Apr 30;43(4):205-15
pubmed: 21389766
Nat Med. 2009 Feb;15(2):159-68
pubmed: 19136964
Mol Endocrinol. 2006 Apr;20(4):844-56
pubmed: 16339272
Mol Cell Biol. 2019 May 14;39(11):
pubmed: 30936246
J Nutr Biochem. 2017 Feb;40:194-200
pubmed: 27936456
Mol Cell Biol. 1999 Sep;19(9):6286-96
pubmed: 10454575
Methods Enzymol. 2014;538:49-65
pubmed: 24529433
Genes Dev. 2000 Nov 15;14(22):2831-8
pubmed: 11090131
J Clin Invest. 2003 Dec;112(12):1796-808
pubmed: 14679176
Nature. 2000 Apr 6;404(6778):635-43
pubmed: 10766250
Cell Metab. 2005 Jan;1(1):27-39
pubmed: 16054042
J Biol Chem. 2004 Jul 16;279(29):30490-7
pubmed: 15136565