Functional plasticity of adipose-derived stromal cells during development of obesity

Xiang Yang Zhu, Shuangtao Ma, Alfonso Eirin, John R. Woollard, Latonya J. Hickson, Dong Sun, Amir Lerman, Lilach O. Lerman

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Obesity is a major risk factor for a number of chronic diseases, including diabetes, cardiovascular diseases, and cancer. Expansion of the adipose mass requires adipocyte precursor cells that originate from multipotent adipose-derived stromal cells (ASCs), which in turn also participate in repair activities. ASC function might decline in a disease milieu, but it remains unclear whether ASC function varies during the development of obesity. We tested the hypothesis that microenvironmental inflammatory changes during development of metabolic disorders in obesity affect ASC function. Domestic pigs were fed with an atherogenic (n=7) or normal (n = 7) diet for 16 weeks. Abdominal adipose tissue biopsies were collected after 8, 12, and 16 weeks of diet for ASC isolation and immunohistochemistry of in situ ASCs and tumor necrosis factor-α (TNF-α). Longitudinal changes in proliferation, differentiation, and anti-inflammatory functions of ASCs were assessed. At 16 weeks, upregulated TNF-α expression in adipose tissue from obese pigs was accompanied by increased numbers of adipocyte progenitors (CD24+/CD34+) in adipose tissue and enlarged adipocyte size. In vitro, ASCs from obese pigs showed enhanced adipogenic and osteogenic propensity, which was abolished by anti-TNF-αtreatment, whereas lean ASCs treated with TNF-α showed enhanced adipogenesis. Furthermore, obese ASCs showed increased senescence compared with lean ASCs, whereas their immunomodulatory capacity was preserved. Adipose tissue inflammation promotes an increase in resident adipocyte progenitors and upregulated TNF-α enhances ASC adipogenesis. Thus, adipose tissue anti-inflammatory strategies might be a novel target to attenuate obesity and its complications.

Original languageEnglish (US)
Pages (from-to)893-900
Number of pages8
JournalStem Cells Translational Medicine
Volume5
Issue number7
DOIs
StatePublished - 2016

Keywords

  • Adipose tissue
  • Inflammation
  • Mesenchymal stem cells
  • Obesity

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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