The Adipose Tissue Microenvironment Regulates Depot-Specific Adipogenesis in Obesity.
The sexually dimorphic distribution of adipose tissue influences the development of obesity-associated pathologies. The accumulation of visceral white adipose tissue (VWAT) that occurs in males is detrimental to metabolic health, while accumulation of subcutaneous adipose tissue (SWAT) seen in females may be protective. Here, we show that adipocyte hyperplasia contributes directly to the differential fat distribution between the sexes. In male mice, high-fat diet (HFD) induces adipogenesis specifically in VWAT, while in females HFD induces adipogenesis in both VWAT and SWAT in a sex hormone-dependent manner. We also show that the activation of adipocyte precursors (APs), which drives adipocyte hyperplasia in obesity, is regulated by the adipose depot microenvironment and not by cell-intrinsic mechanisms. These findings indicate that APs are plastic cells, which respond to both local and systemic signals that influence their differentiation potential independent of depot origin. Therefore, depot-specific AP niches coordinate adipose tissue growth and distribution.
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
Elise
E
Jeffery
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Allison
A
Wing
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Brandon
B
Holtrup
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Zachary
Z
Sebo
Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Jennifer L
JL
Kaplan
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Rocio
R
Saavedra-Peña
Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Christopher D
CD
Church
Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Laura
L
Colman
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Ryan
R
Berry
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA; Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: matthew.rodeheffer@yale.edu.
Matthew S
MS
Rodeheffer
D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D050156:Adipogenesis; D000273:Adipose Tissue / Q000502:physiology*; D052436:Adipose Tissue, White / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D005260:Female; D006965:Hyperplasia; D008297:Male; D051379:Mice; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size; D012727:Sex Characteristics