Wnt signaling activation in adipose progenitors promotes insulin-independent muscle glucose uptake

Daniel Zeve, Jin Seo, Jae Myoung Suh, Drew Stenesen, Wei Tang, Eric D. Berglund, Yihong Wan, Linda J. Williams, Ajin Lim, Myrna J. Martinez, Renée M. McKay, Douglas P. Millay, Eric N. Olson, Jonathan M. Graff

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)492-504
Number of pages13
JournalCell Metabolism
Volume15
Issue number4
DOIs
StatePublished - Apr 4 2012

Fingerprint

Fats
Insulin
Lipodystrophy
Glucose
Muscles
AMP-Activated Protein Kinases
Catenins
Peroxisome Proliferator-Activated Receptors
Facilitative Glucose Transport Proteins
Subcutaneous Fat
Conditioned Culture Medium
Insulin Resistance
Blood Glucose
Adipose Tissue
Hormones
Food
Serum
Therapeutics

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Wnt signaling activation in adipose progenitors promotes insulin-independent muscle glucose uptake. / Zeve, Daniel; Seo, Jin; Suh, Jae Myoung; Stenesen, Drew; Tang, Wei; Berglund, Eric D.; Wan, Yihong; Williams, Linda J.; Lim, Ajin; Martinez, Myrna J.; McKay, Renée M.; Millay, Douglas P.; Olson, Eric N.; Graff, Jonathan M.

In: Cell Metabolism, Vol. 15, No. 4, 04.04.2012, p. 492-504.

Research output: Contribution to journalArticle

Zeve, Daniel ; Seo, Jin ; Suh, Jae Myoung ; Stenesen, Drew ; Tang, Wei ; Berglund, Eric D. ; Wan, Yihong ; Williams, Linda J. ; Lim, Ajin ; Martinez, Myrna J. ; McKay, Renée M. ; Millay, Douglas P. ; Olson, Eric N. ; Graff, Jonathan M. / Wnt signaling activation in adipose progenitors promotes insulin-independent muscle glucose uptake. In: Cell Metabolism. 2012 ; Vol. 15, No. 4. pp. 492-504.
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