Wnt Signaling Activation in Adipose Progenitors Promotes Insulin-Independent Muscle Glucose Uptake

SummaryAdipose 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.

Graphical AbstractFigure optionsDownload high-quality image (192 K)Download as PowerPoint slideHighlights
► β-catenin activation in fat progenitors induces a fibroblastic cell fate change
► Lipodystrophic PBCA mice lack fat but have improved glucose homeostasis
► Glucose uptake is increased in muscles of PBCA mice in an insulin-independent manner
► Adipose progenitors secrete a glucose regulatory factor in response to Wnt activation