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Title: Methyl-ß-cyclodextrin alters adipokine gene expression and glucose metabolism in swine adipose tissue

Author
item Ramsay, Timothy
item Blomberg, Le Ann
item Caperna, Thomas

Submitted to: Animal-The International Journal of Animal Biosciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/14/2013
Publication Date: 7/23/2014
Citation: Ramsay, T.G., Blomberg, L., Caperna, T.J. 2014. Methyl-ß-cyclodextrin alters adipokine gene expression and glucose metabolism in swine adipose tissue. Animal-The International Journal of Animal Biosciences. 7(10):1690-1696.

Interpretive Summary: Stress has a major impact on the performance of growing swine. Stress can originate from interaction with the environment, from interactions with other animals, or even internally. This internal stress can result from fighting infection or from changes in the diet which affect digestion and metabolism. Metabolic stress can impact the growth of the young pig. This is especially important as variability in growth rate in baby pigs results in litters of animals that are weaned at a great variety of body weights. This variability is an inherent inefficiency in swine production as the weaning weight has a direct impact on the efficiency of animal growth and lean meat deposition. Identification of the mechanisms that are responsible for this variability and the development of markers to reduce this variability in growth rate within a litter of pigs have a direct impact on the economics of swine production and agricultural efficiency. This study examined the effect of metabolic stress on adipose (fat) tissue metabolism and gene expression. Adipose tissue is a critical tissue for the survival of the baby pig since it is the major source of energy for survival. Adipose tissue from 21 day old pigs was incubated with a compound (methyl-ß-cyclodextrin or MCD) that removes cholesterol from the cell surface and thus alters the ability of the cell to function; thereby inducing a metabolic stress. Treatment with MCD resulted in the tissue becoming less capable of making fat when stimulated by insulin; this metabolic stress caused an insulin resistance, which was determined to be partially due to the production of a protein called tumor necrosis factor. The metabolic stress caused the adipose tissue to make and release tumor necrosis factor which contributed to producing an insulin resistance within the adipose tissue and making the tissue less efficient at fat storage. These data demonstrate that metabolic stress alters growth of adipose tissue by affecting the tissue’s ability to make fat. Secondly, the adipose tissue responds to the metabolic stress by producing factors that limit this growth even more. Lastly, these data suggests that tumor necrosis factor may be an good biomarker for identifying metabolic stress in young growing pigs.

Technical Abstract: This study was designed to determine if metabolic stress as induced by methyl-ß-cyclodextrin (MCD) can alter cytokine expression in neonatal swine adipose tissue explants. 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 37ºC. The medium also contained BSA or MCD at 0, 0.05, 0.1, 0.2 or 0.3%. Tissue explants were treated with these media for one hour and then all were switched to the same basal incubation medium containing 0.05% BSA. Explants were removed from the basal medium at 2 or 8 h of incubation and real-time PCR was performed to assess expression of tumor necrosis a (TNFa) and interleukin 6 (IL6), acetyl CoA carboxylase (CBX) and fatty acid synthase (FAS). 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 TNFa mRNA abundance (P < 0.01). Treatment with MCD increased TNFa mRNA mRNA abundance by up to 8 fold (P < 0.009) while IL6 gene expression increased a hundredfold (P < 0.001) with a suppression in CBX and FAS expression (P < 0.01). This was paralleled by MCD inhibition of insulin stimulated glucose oxidation and lipogenesis (P < 0.001). However, addition of a TNFa antibody to the incubation medium alleviated this inhibition of insulin stimulated glucose metabolism by approximately 30% (P < 0.05).