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expression in
obese women: relationship to hyperinsulinemia
1 Equipe Accueil 2402, Université Henri-Poincaré, 54500 Vandoeuvre les Nancy; 2 Institut National de la Santé et de la Recherche Médicale Unité 449, Faculté de Médecine Laënnec, 69000 Lyon, France; 3 Service de Diabétologie, Maladies Métaboliques et Nutrition and 4 Centre d'Investigation Cliniques Inserm-Centre Hospitalier Universitaire de Nancy, 54520 Dommartin les Toul, France
We have shown that
membrane sphingomyelin (SM) is an independent predictor of the variance
of fasting plasma insulin (FPI) concentrations and the homeostasis
model assessment (HOMA) estimate of insulin resistance in obese women.
The peroxisome proliferator-activated receptor-
(PPAR-) is a key
component in adipocyte differentiation that may also contribute to the
sensitivity of cells to insulin. PPAR- is activated by fatty acids,
and the membrane composition may have an impact on the activity of
PPAR- and thus on the sensitivity of adipocytes to insulin. We
investigated these possible links by determining the phospholipid
contents of adipocyte membranes, the mRNA expression of PPAR-, and
the FPI and HOMA estimate of insulin resistance in obese women. The
mRNA levels of tumor necrosis factor-
(TNF-), which is suspected
to play a role in insulin resistance and which downregulates PPAR-
expression, were also quantified. FPI and HOMA were strongly positively
correlated with membrane SM (P < 0.005) and cholesterol
(P < 0.005). PPAR- mRNA levels were negatively
correlated with FPI (P < 0.05) and HOMA (P
< 0.05) and positively correlated with high-density lipoprotein (HDL) cholesterol (P < 0.05), membrane SM (P < 0.05), and cholesterol contents (P < 0.05). TNF- mRNA
levels were not correlated with membrane parameters. In stepwise
multiple regression analysis, the variations in PPAR- mRNA levels
were mainly explained by HDL cholesterol (31.9%) and membrane SM
(17.7%). Our study shows that the expression of PPAR-, a major
factor controlling adipocyte functions, the lipid composition of the
membrane, and insulin sensitivity are probably closely associated in
the adipose tissue of obese women.
obesity; adipose tissue; plasma membrane; transcription factor; insulin resistance
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