Show simple item record

AuthorLiu, X.
AuthorMalki, A.
AuthorCao, Y.
AuthorLi, Y.
AuthorQian, Y.
AuthorWang, X.
AuthorChen, X.
Available date2024-03-31T04:23:36Z
Publication Date2015-05-26
Publication NameExperimental and Clinical Endocrinology and Diabetes
Identifierhttp://dx.doi.org/10.1055/s-0035-1548789
CitationLiu, X., Malki, A., Cao, Y., Li, Y., Qian, Y., Wang, X., & Chen, X. (2015). Glucose-and Triglyceride-lowering Dietary Penta-O-galloyl--D-Glucose Reduces Expression of PPAR and C/EBP, Induces p21-Mediated G1 Phase Cell Cycle Arrest, and Inhibits Adipogenesis in 3T3-L1 Preadipocytes. Experimental and Clinical Endocrinology & Diabetes, 123(5), 308-316.
ISSN0947-7349
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84930212703&origin=inward
URIhttp://hdl.handle.net/10576/53729
AbstractPlant polyphenols, such as hydrolysable tannins, are present in the human diet and known to exhibit anti-diabetic and anti-obesity activity. We previously reported that the representative hydrolysable tannin compound α-penta-galloyl-glucose (α-PGG) is a small molecule insulin mimetic that, like insulin, binds to insulin receptor (IR) and activates the IR-Akt-GLUT4 signaling pathway to trigger glucose transport and reduce blood glucose levels in db/db and ob/ob diabetic mice. However, its effects on adipogenesis and lipid metabolism were not known. In this study, high fat diet (HFD)-induced diabetic and obese mice were treated with α-PGG to determine its effects on blood glucose and triglycerides. 3T3-L1 preadipocytes were used as a cell model for identifying the anti-adipogenic activity of α-PGG at molecular and cellular levels as a first step in elucidating the mechanism of action of the compound. In vivo, oral administration of α-PGG significantly reduced levels of blood glucose, triglyceride, and insulin in HFD-induced diabetic/obese mice (P<0.05). In vitro, α-PGG inhibited the differentiation of 3T3-L1 preadipocytes into mature adipocytes. α-PGG suppressed the expression of positive adipogenic factors PPARγ C/EBPα and mTOR and augmented the negative adipogenic factor Pref-1. Furthermore, α-PGG induced upregulation of p21 and G1 phase cell cycle arrest. In contrast, adipogenic signaling pathways mediated by insulin, the cAMP response element binding protein (CREB) and glucocorticoid receptor (GR), were not inhibited. RNAi knockdown of p21 led to a 4-fold increase in triglyceride level in 3T3-L1 preadipocytes treated with MDI and α-PGG compared to regular preadipocytes. These results indicate, for the first time, that α-PGG is blood triglyceride- and glucose-lowering in HFD-induced obese and diabetic mice. It selectively inhibited some but not all major adipogenic pathways as well as the mTOR-p21-mediated cell cycle regulatory pathway. It is very likely that these apparently diverse but coordinated activities together inhibited adipogenesis. These results expand our knowledge on how PGG works in adipocytes and further confirm that α-PGG functions as an orally-deliverable natural insulin mimetic with adipogenetic modulatory functions.
Sponsor- National Science Foundation - grant No. [IIP-0227907].
Languageen
PublisherThieme
Subjecthydrolyzable tannins
insulin mimetic
nutritional sciences
obesity
type 2 diabetes mellitus
TitleGlucose- and triglyceride-lowering dietary penta-O-galloyl-α-D-glucose reduces expression of PPARγ and C/EBPα, induces p21-Mediated G1 phase cell cycle arrest, and inhibits adipogenesis in 3T3-L1 preadipocytes
TypeArticle
Pagination308-316
Issue Number5
Volume Number123
dc.accessType Abstract Only


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record