Elsevier

Molecular Metabolism

Volume 16, October 2018, Pages 160-171
Molecular Metabolism

Brief Communication
TGF-β receptor 1 regulates progenitors that promote browning of white fat

https://doi.org/10.1016/j.molmet.2018.07.008Get rights and content
Under a Creative Commons license
open access

Highlights

  • Loss of TβRI in adipose tissue promotes beige adipogenesis.

  • TβRI regulates presumptive beige adipocyte progenitors in white fat.

  • TβRI signals interact with the PGE2/Cox2 pathway during beige adipogenesis.

  • TβRI regulates thermogenesis, mitochondrial bioenergetics and beige adipogenesis.

Abstract

Objective

Beige/brite adipose tissue displays morphological characteristics and beneficial metabolic traits of brown adipose tissue. Previously, we showed that TGF-β signaling regulates the browning of white adipose tissue. Here, we inquired whether TGF-β signals regulated presumptive beige progenitors in white fat and investigated the TGF-β regulated mechanisms involved in beige adipogenesis.

Methods

We deleted TGF-β receptor 1 (TβRI) in adipose tissue (TβRIAdKO mice) and, using flow-cytometry based assays, identified and isolated presumptive beige progenitors located in the stromal vascular cells of white fat. These cells were molecularly characterized to examine beige/brown marker expression and to investigate TGF-β dependent mechanisms. Further, the cells were transplanted into athymic nude mice to examine their adipogenesis potential.

Results

Deletion of TβRI promotes beige adipogenesis while reducing the detrimental effects of high fat diet feeding. Interaction of TGF-β signaling with the prostaglandin pathway regulated the appearance of beige adipocytes in white fat. Using flow cytometry techniques and stromal vascular fraction from white fat, we isolated presumptive beige stem/progenitor cells (iBSCs). Upon genetic or pharmacologic inhibition of TGF-β signaling, these cells express high levels of predominantly beige markers. Transplantation of TβRI-deficient stromal vascular cells or iBSCs into athymic nude mice followed by high fat diet feeding and stimulation of β-adrenergic signaling via CL316,243 injection or cold exposure promoted robust beige adipogenesis in vivo.

Conclusions

TβRI signals target the prostaglandin network to regulate presumptive beige progenitors in white fat capable of developing into beige adipocytes with functional attributes. Controlled inhibition of TβRI signaling and concomitant PGE2 stimulation has the potential to promote beige adipogenesis and improve metabolism.

Graphical abstract

Wankhade et al. show that loss of TβRI in adipose tissue promotes beige adipogenesis. Interaction between the TGF-β and prostaglandin pathways regulates presumptive progenitors in white fat that develop into beige adipocytes with functional attributes. These findings provide mechanistic insight into signals regulating beige adipogenesis.

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Keywords

Beige/brite adipogenesis
Progenitors
Metabolism
Diabetes
Obesity
TGF-beta
Prostaglandin E2
Cyclooxygenase 2

Cited by (0)

6

Present address: Arkansas Children's Nutrition Center, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, 72202, USA.

7

Present address: Center for Diabetes, Obesity and Metabolism, Department of Internal Medicine, Wake Forest University, School of Medicine, Winston-Salem, NC, USA.