title: Methyl-β-cyclodextrin alters adipokine gene expression and glucose metabolism in swine adipose tissue.
abstract: This study was designed to determine whether methyl-β-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 (100 ± 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 37°C. 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 α (TNF) and interleukin 6 (IL6), acetyl CoA carboxylase (ACAC) and fatty acid synthase (FASN). Alternatively, rates of 14C-glucose oxidation and lipogenesis were monitored ± 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).
authors.affiliation: Animal Biosciences and Biotechnology Laboratory, Animal and Natural Resources Institute, USDA/ARS, Beltsville Agricultural Research Center, USDA, Beltsville, MD 20705, USA. timothy.ramsay@ars.usda.gov
authors.forename: T G
authors.initials: TG
authors.lastname: Ramsay
authors.forename: L
authors.initials: L
authors.lastname: Blomberg
authors.forename: T J
authors.initials: TJ
authors.lastname: Caperna
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D013552:Swine / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology*
chemical_list: D054392:Adipokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D005947:Glucose