Abstract
Adipose tissue hyperplasia with increased number of adipocytes is implicated in a protective rather than deleterious effect on obesity-associated metabolic disorder. It is poorly understood how the adipose tissue cellularity is regulated. Tc1 is a gene of vertebrates that regulates diverse downstream genes. Young Tc1-deleted mice fed on standard chow diet show expanded adipose tissue with smaller adipocytes in size compared to wild type controls, representing adipose tissue hyperplasia. Tc1−/− mice show enhanced glucose tolerance and reduced serum lipids. Adipocyte-derived stem cells (ADSCs) from Tc1−/− mice show enhanced proliferative and adipogenic capacity compared to wild type controls, suggesting that the adipose hyperplasia is regulated at the stem cell level. PPARγ and CEBPα are up-regulated robustly in Tc1−/− ADSCs upon induction for adipogenesis. Wisp2 and Dlk1, inhibitors of adipogenesis, are down-regulated in Tc1−/− ADSCs compared to controls. Tc1-transfected NIH3T3 cells show higher β-catenin reporter signals than vector transfected controls, suggesting a role of canonical Wnt signaling in the Tc1-dependent adipose regulation. Our data support that Tc1 is a novel regulator for adipose stem cells. Adipose tissue hyperplasia may be implicated in the metabolic regulation of Tc1−/− mice.
Highlights
IntroductionIt activates endothelial cells enhancing classical NF-κB signaling[28]
We have reported previously that Tc1-deleted mice show increased white cells in peripheral blood and enhanced hematopoietic activity[29]
We investigated the role of Tc1 for the signaling with TOPFLASH reporter system in NIH3T3 cell that has adipogenic stem cell-like potential
Summary
It activates endothelial cells enhancing classical NF-κB signaling[28]. In zebrafish embryo, which has 2 homologues, they are expressed in association with blood vessels or hematopoietic cells[28]. We have reported previously that Tc1-deleted mice show increased white cells in peripheral blood and enhanced hematopoietic activity[29]. We report a novel biological role of Tc1 in adipose tissue, stem cell, and metabolic regulation
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