GM3 ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of insulin resistance in obese women.
OBJECTIVE
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, 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, phosphatidylethanolamine methyl transferase (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.


CONCLUSIONS
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-α, 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.
Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Monash University Centre for Obesity Research and Education, Melbourne, Victoria, Australia.
J M
JM
Wentworth
Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
G
G
Naselli
Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
K
K
Ngui
Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Mathematics and Statistics, University of Melbourne, Carlton, Victoria, Australia.
G K
GK
Smyth
Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
R
R
Liu
Monash University Centre for Obesity Research and Education, Melbourne, Victoria, Australia.
P E
PE
O'Brien
Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Victoria, Australia.
C
C
Bruce
Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
J
J
Weir
Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
M
M
Cinel
Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
P J
PJ
Meikle
Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
L C
LC
Harrison
D017667:Adipocytes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005679:G(M3) Ganglioside / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D005679:G(M3) Ganglioside; D008055:Lipids; D010714:Phosphatidylethanolamines; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C483858:phosphatidylethanolamine