G<sub>M3</sub> ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of human insulin resistance — ASN Events
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  3. GM3 ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of human insulin resistance

GM3 ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of human insulin resistance (#238)

John M Wentworth 1 , Paul E O'Brien 2 , Clinton Bruce 3 , Peter Meikle 4 , Leonard C Harrison 1
  1. WEHI, Parkville, VIC, Australia
  2. Monash University Centre for Obesity Research and Education, Prahran, Australia
  3. Deakin University, Melbourne
  4. Baker-IDI heart and diabetes institute, Melbourne, Australia

Aims

The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance.

Methods

Subcutaneous and omental adipose tissue and serum were obtained from 29 obese non-diabetic women, 13 of whom were hyperinsulinemic. Histology, and lipid and gene profiling were performed.

Results

In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, PEMT, decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum.

Interpretation

The relevance of these findings to insulin resistance in humans is supported by published mouse studies in which adipocyte GM3 ganglioside, increased by the inflammatory cytokine tumour necrosis factor-a, impaired insulin action, and PEMT was required for adipocyte lipid storage. Thus, in visceral adipose tissue of obese humans, an increase in GM3 ganglioside secondary to inflammation may contribute to insulin resistance and a decrease in PEMT may be a compensatory response to adipocyte hypertrophy.