title: Curcumin represses mouse 3T3-L1 cell adipogenic differentiation via inhibiting miR-17-5p and stimulating the Wnt signalling pathway effector Tcf7l2.
abstract: Understanding mechanisms underlying adipogenic differentiation may lead to the discovery of novel therapeutic targets for obesity. Wnt signalling pathway activation leads to repressed adipogenic differentiation while certain microRNAs may regulate pre-adipocyte proliferation and differentiation. We show here that in mouse white adipose tissue, miR-17-5p level is elevated after high fat diet consumption. miR-17-5p upregulates adipogenic differentiation, as its over-expression increased while its inhibition repressed 3T3-L1 differentiation. The Tcf7l2 gene encodes a key Wnt signalling pathway effector, and its human homologue TCF7L2 is a highly regarded diabetes risk gene. We found that Tcf7l2 is an miR-17-5p target and confirmed the repressive effect of Tcf7l2 on 3T3-L1 adipogenic differentiation. The natural plant polyphenol compound curcumin possesses the body weight lowering effect. We observed that curcumin attenuated miR-17-5p expression and stimulated Tcf7l2 expression in 3T3-L1 cells. These, along with the elevation of miR-17-5p expression in mouse epididymal fat tissue in response to high fat diet consumption, allowed us to suggest that miR-17-5p is among central switches of adipogenic differentiation. It activates adipogenesis via repressing the Wnt signalling pathway effector Tcf7l2, and its own expression is likely nutritionally regulated in health and disease.
authors.affiliation: Toronto General Research Institutes, University Health Network, Toronto, Canada.|Department of Physiology, University of Toronto, Toronto, Canada.|Banting and Best Diabetes Center, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Lili
authors.initials: L
authors.lastname: Tian
authors.affiliation: Toronto General Research Institutes, University Health Network, Toronto, Canada.|Department of Physiology, University of Toronto, Toronto, Canada.|Banting and Best Diabetes Center, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Zhuolun
authors.initials: Z
authors.lastname: Song
authors.affiliation: Toronto General Research Institutes, University Health Network, Toronto, Canada.|Banting and Best Diabetes Center, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Shao
authors.affiliation: Sunnybrook Research Institute, University of Toronto, Toronto, Canada.
authors.forename: William W
authors.initials: WW
authors.lastname: Du
authors.affiliation: Toronto General Research Institutes, University Health Network, Toronto, Canada.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Zhao
authors.affiliation: Toronto General Research Institutes, University Health Network, Toronto, Canada.
authors.forename: Kejing
authors.initials: K
authors.lastname: Zeng
authors.affiliation: Sunnybrook Research Institute, University of Toronto, Toronto, Canada.
authors.forename: Burton B
authors.initials: BB
authors.lastname: Yang
authors.affiliation: Toronto General Research Institutes, University Health Network, Toronto, Canada.|Department of Physiology, University of Toronto, Toronto, Canada.|Banting and Best Diabetes Center, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Tianru
authors.initials: T
authors.lastname: Jin
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse; C544895:Tcf7l2 protein, mouse; D058118:Transcription Factor 7-Like 2 Protein; D003474:Curcumin