Methyl-b-cyclodextrin alters adipokine gene expression and glucose metabolism in swine adipose tissue*

This study was designed to determine whether methyl-b-cyclodextrin (MCD) can substitute for albumin in incubation medium for neonatal swine adipose tissue explants, or whether MCD affects metabolism and cytokine expression. Subcutaneous adipose tissue explants (1006 10 mg) were prepared from 21-day-old pigs. Explants were incubated in medium 199 supplemented with 25 mM HEPES, 1.0 nM insulin at 378C. The medium also contained bovine serum albumin (BSA) or MCD at 0%, 0.05%, 0.1%, 0.2% or 0.3%. Tissue explants were treated with these media for 1 h and then switched to the same basal incubation medium containing 0.05% BSA. Explants were removed from basal medium at 2 or 8 h of incubation, and real-time PCR was performed to assess expression of tumor necrosis a (TNF) and interleukin 6 (IL6), acetyl CoA carboxylase (ACAC) and fatty acid synthase (FASN). Alternatively, rates of C-glucose oxidation and lipogenesis were monitored6 insulin (100 nM), following MCD treatment. Incubation with BSA had minimal effects on gene expression or adipose tissue metabolism, only producing a doubling in TNF mRNA abundance ( P, 0.01). Treatment with MCD increased TNF mRNA abundance by eightfold ( P, 0.009), whereas IL6 gene expression increased a 100-fold ( P, 0.001) with a suppression in ACAC and FASN expression ( P, 0.01). This was paralleled by MCD inhibition of insulin-stimulated glucose oxidation and lipogenesis ( P, 0.001). Addition of a TNF antibody to the incubation medium alleviated this inhibition of insulin-stimulated glucose metabolism by ,30% ( P, 0.05).