Body composition changes and inhibition of fat development in vivo implicates androgen in regulation of stem cell lineage allocation

Anthony A. Semirale, Xiao Wei Zhang, Kristine Wiren

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Androgens regulate body composition in youth and declining testosterone that occurs with aging is associated with muscle wasting, increased fat mass and osteopenia. Transgenic mice with targeted androgen receptor (AR) over-expression in mesenchymal stem cells (MSC) were generated to explore the role of androgen signaling in the regulation of body composition. Transgenic males, but not females, were shorter and have reduced body weight and visceral fat accumulation. Dual-energy X-ray absorptiometry (DXA) revealed significant reductions in fat mass with a reciprocal increase in lean mass, yet no difference in food consumption or locomotor activity was observed. Adipose tissue weight was normal in brown fat but reduced in both gonadal and perirenal depots, and reduced hyperplasia was observed with smaller adipocyte size in visceral and subcutaneous white adipose tissue. Although serum leptin, adiponectin, triglyceride, and insulin levels were no different between the genotypes, intraperitoneal glucose tolerance testing (IPGTT) showed improved glucose clearance in transgenic males. High levels of the AR transgene are detected in MSCs but not in mature fat tissue. Reduced fibroblast colony forming units indicate fewer progenitor cells resident in the marrow in vivo. Precocious expression of glucose transporter 4 (GLUT4), peroxisome proliferator-activated receptor γ (PPARγ), and CCAAT enhancer-binding protein a (C/EBPα) was observed in proliferating precursor cultures from transgenic mice compared to controls. In more mature cultures, there was little difference between the genotypes. We propose a mechanism where enhanced androgen sensitivity can alter lineage commitment in vivo to reduce progenitor number and fat development, while increasing the expression of key factors to promote smaller adipocytes with improved glucose clearance.

Original languageEnglish (US)
Pages (from-to)1773-1786
Number of pages14
JournalJournal of Cellular Biochemistry
Volume112
Issue number7
DOIs
StatePublished - Jul 2011

Fingerprint

Cell Lineage
Body Composition
Stem cells
Androgens
Stem Cells
Fats
Androgen Receptors
Chemical analysis
Adipocytes
Glucose
Transgenic Mice
Genotype
Tissue
CCAAT-Enhancer-Binding Proteins
White Adipose Tissue
Peroxisome Proliferator-Activated Receptors
Brown Adipose Tissue
Intra-Abdominal Fat
Facilitative Glucose Transport Proteins
Metabolic Bone Diseases

Keywords

  • Adipogenesis
  • Androgen Receptor
  • Body Composition
  • Lean Mass
  • Msc
  • Testosterone

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Body composition changes and inhibition of fat development in vivo implicates androgen in regulation of stem cell lineage allocation. / Semirale, Anthony A.; Zhang, Xiao Wei; Wiren, Kristine.

In: Journal of Cellular Biochemistry, Vol. 112, No. 7, 07.2011, p. 1773-1786.

Research output: Contribution to journalArticle

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