Adipocyte membrane phospholipids and PPAR-γ expression in obese women: relationship to hyperinsulinemia

Abstract

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-gamma (PPAR-gamma) is a key component in adipocyte differentiation that may also contribute to the sensitivity of cells to insulin. PPAR-gamma is activated by fatty acids, and the membrane composition may have an impact on the activity of PPAR-gamma 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-gamma, and the FPI and HOMA estimate of insulin resistance in obese women. The mRNA levels of tumor necrosis factor-alpha (TNF-alpha), which is suspected to play a role in insulin resistance and which downregulates PPAR-gamma expression, were also quantified. FPI and HOMA were strongly positively correlated with membrane SM (P < 0.005) and cholesterol (P < 0.005). PPAR-gamma 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-alpha mRNA levels were not correlated with membrane parameters. In stepwise multiple regression analysis, the variations in PPAR-gamma mRNA levels were mainly explained by HDL cholesterol (31.9%) and membrane SM (17.7%). Our study shows that the expression of PPAR-gamma, 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.

Dietary conjugated linolenic acid in relation to CLA differently modifies body fat mass and serum and liver lipid levels in rats

“…PPAR-γ is known to play an important role for the differentiation of adipocytes (43,44). Recently, studies in obese women showed that PPAR-γ mRNA levels in adipose tissue were positively associated with the serum concentrations of HDL-cholesterol (45,46). Serum HDL-cholesterol concentrations were also shown to exhibit a positive correlation with leptin mRNA levels in adipose tissue (45).…”

A Role for Sphingolipids in Producing the Common Features of Type 2 Diabetes, Metabolic Syndrome X, and Cushing’s Syndrome

“…Conversely, sphingolipids have been shown to antagonize the effects of PPAR-␥. Specifically, sphingomyelin downregulates PPAR-␥ gene expression in 3T3-F442 adipocytes and is an independent predictor of insulin resistance in obese women (184,185). Ceramide has similarly been shown to inhibit PPAR-␥ expression (186).…”

Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment

“…Membrane fraction was prepared as described previously ( 16 ), with minor modifi cations. Briefl y, cells were lysed in 0.25 M sucrose buffer, containing 1 mM deoxycholate with both protease and phosphatase inhibitors, and then homogenized.…”