Depot-specific differences in adipogenic progenitor abundance and proliferative response to high-fat diet.
White adipose tissue (fat) is the primary organ for energy storage and its regulation has serious implications on human health. Excess fat tissue causes significant morbidity, and adipose tissue dysfunction caused by excessive adipocyte hypertrophy has been proposed to play a significant role in the pathogenesis of metabolic disease. Studies in both humans and animal models show that metabolic dysfunction is more closely associated with visceral than subcutaneous fat accumulation. Here, we show that in mice fed a high-fat diet, visceral fat (VAT) grows mostly by hypertrophy and subcutaneous fat (SAT) by hyperplasia, providing a rationale for the different effects of specific adipose depots on metabolic health. To address whether depot expansion is controlled at the level of stem/progenitor cells, we developed a strategy to prospectively identify adipogenic progenitors (APs) from both depots. Clonogenic assays and in vivo bromodeoxyuridine (BrdU) studies show that APs are eightfold more abundant in SAT than VAT, and that AP proliferation is significantly increased in SAT but not VAT in response to high-fat diet. Our results suggest that depot-specific differences in AP abundance and proliferation underlie whether a fat depot expands by hypertrophy or hyperplasia, and thus may have important implications on the development of metabolic disease. In addition, we provide the first evidence that dietary inputs can modulate the proliferation of adipogenic progenitors in adults.
Joe
Aaron W B
AW
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Yi
Lin
L
Even
Yasmine
Y
Vogl
A Wayne
AW
Rossi
Fabio M V
FM
D017667:Adipocytes / Q000166:cytology* / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology* / Q000503:physiopathology; D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D004041:Dietary Fats / Q000009:adverse effects* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005526:Food, Formulated / Q000009:adverse effects*; D006965:Hyperplasia / Q000209:etiology / Q000503:physiopathology; D006984:Hypertrophy / Q000209:etiology / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
D004041:Dietary Fats; D001973:Bromodeoxyuridine