title: Wnt signaling activation in adipose progenitors promotes insulin-independent muscle glucose uptake.
abstract: Adipose tissues provide circulating nutrients and hormones. We present in vivo mouse studies highlighting roles for Wnt signals in both aspects of metabolism. β-catenin activation in PPARγ-expressing fat progenitors (PBCA) decreased fat mass and induced fibrotic replacement of subcutaneous fat specifically. In spite of lipodystrophy, PBCA mice did not develop the expected diabetes and hepatosteatosis, but rather exhibited improved glucose metabolism and normal insulin sensitivity. Glucose uptake was increased in muscle independently of insulin, associated with cell-surface translocation of glucose transporters and AMPK activation. Ex vivo assays showed these effects were likely secondary to blood-borne signals since PBCA sera or conditioned media from PBCA fat progenitors enhanced glucose uptake and activated AMPK in muscle cultures. Thus, adipose progenitor Wnt activation dissociates lipodystrophy from dysfunctional metabolism and highlights a fat-muscle endocrine axis, which may represent a potential therapy to lower blood glucose and improve metabolism.
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9133, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zeve
authors.forename: Jin
authors.initials: J
authors.lastname: Seo
authors.forename: Jae Myoung
authors.initials: JM
authors.lastname: Suh
authors.forename: Drew
authors.initials: D
authors.lastname: Stenesen
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Eric D
authors.initials: ED
authors.lastname: Berglund
authors.forename: Yihong
authors.initials: Y
authors.lastname: Wan
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Williams
authors.forename: Ajin
authors.initials: A
authors.lastname: Lim
authors.forename: Myrna J
authors.initials: MJ
authors.lastname: Martinez
authors.forename: Renée M
authors.initials: RM
authors.lastname: McKay
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Millay
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Graff
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002451:Cell Compartmentation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008060:Lipodystrophy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D047495:PPAR gamma / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D007328:Insulin; D047495:PPAR gamma; D051176:beta Catenin; D055372:AMP-Activated Protein Kinases; D005947:Glucose