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Site-specific differences of insulin action in adipose tissue derived from normal prepubertal children

Malcolm Grohmann1, Claire Stewart, Gavin Welsh

  • 1Department of Surgery, University of Bristol, Bristol Royal Infirmary, Upper Maudlin Street, Bristol, UK.

Experimental Cell Research
|June 7, 2005
PubMed

Insights

Childhood fat cells show distinct responses to insulin, varying by location (subcutaneous vs. visceral) and influenced by differentiation and TNFalpha. These differences impact glucose metabolism, crucial for understanding childhood obesity.

Area of Science:

  • Pediatric Endocrinology
  • Metabolic Research
  • Cell Biology

Background:

  • Body fat distribution is linked to obesity-related diseases in adults, but its role in children is less understood.
  • Preadipocytes, the precursors to fat cells, are key in regulating fat tissue metabolism.
  • Understanding differences in fat cell metabolism in children is crucial for addressing pediatric obesity.

Purpose of the Study:

  • To investigate differences in insulin-mediated metabolism between subcutaneous and visceral preadipocytes from prepubertal children.
  • To examine the impact of cell differentiation on these metabolic responses.
  • To assess the effects of Tumor Necrosis Factor alpha (TNFalpha) on preadipocyte metabolism.

Main Methods:

  • Primary cell cultures of subcutaneous and visceral preadipocytes from prepubertal children were established.
  • Cells were analyzed for proliferation rates, insulin signaling (GSK-3 and MAPK phosphorylation), and insulin receptor abundance.
  • Glucose uptake (2-deoxy-glucose transport), GLUT1/4 abundance, and TNFalpha effects were measured before and after differentiation.

Main Results:

  • Subcutaneous preadipocytes exhibited higher proliferation rates than visceral ones.
  • Insulin sensitivity differed between the two cell types, with greater sensitivity in subcutaneous cells.
  • Post-differentiation, visceral adipocytes showed significantly increased GLUT4 abundance and insulin-stimulated glucose transport, further enhanced by TNFalpha.
  • TNFalpha also increased basal glucose transport and GLUT1 localization in both cell types.

Conclusions:

  • Significant site-specific metabolic differences exist between pediatric subcutaneous and visceral fat cells.
  • Insulin response, glucose transport, and the effects of TNFalpha vary with differentiation status and fat depot location.
  • These findings provide insights into the pathophysiology of childhood obesity and fat distribution.

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