Obesity and adipose tissue expansion in Ossabaw swine

Obesity is characterized as a state of chronic low-grade inflammation, which originates in adipose tissue from adipocyte dysfunction as a consequence of adipocyte hypertrophy. Although rodent models have been pivotal to understanding the etiology of obesity and its co-morbidities, and the roles of specific genes, distinct differences between rodents and humans underscore the need for alternative comparative models. Swine are an attractive comparative model because of similar physiology and anatomy with humans. Ossabaw swine are of particular interest due to their "thrifty" genotype and predisposition to multiple risk factors for the metabolic syndrome.;We first used Ossabaw swine to investigate the effects of high saturated fat and high saturated fat plus n-3 fatty acids on adipose tissue macrophages, inflammation, and insulin resistance. In this study, despite severe obesity, Ossabaw swine did not develop systemic inflammation. Consumption of the high palm oil diet did decrease serum adiponectin, and this decrease was attenuated by the addition of n-3 fatty acids to the diet. Additionally, we determined that the majority of adipose tissue macrophages are of an anti-inflammatory phenotype. High dietary palm oil did increase the percentage of inflammatory macrophages, and this increase was attenuated by the addition of n-3 fatty acids. Finally, the consumption of high palm oil induced insulin resistance, which was attenuated by the addition of n-3 fatty acids. Thus, in Ossabaw swine, morbid obesity induces insulin resistance, but insulin resistance is not linked to inflammation.;Obesity in humans and rodents causes an increase in subcutaneous adipocyte size of ∼2 to 3 fold. Ossabaw subcutaneous adipocyte size was increased ∼4.3 fold due to the consumption of a diet high in fat. Because of marked adipocyte hypertrophy coupled with the lack of inflammation in obese Ossabaw adipocytes, we sought to determine if Ossabaw adipocytes were protected against saturated fatty acid-induced inflammation. Therefore, we investigated the differences between Ossabaw and Yorkshire stromal vascular cell-derived adipocytes with respect to differentiation and palmitate-induced inflammation and insulin resistance. In this study, we determined that Ossabaw adipocytes express more peroxisome proliferator-activated receptor gamma, have more glycerol-3-phosphate dehydrogenase activity, and higher rates of clonal expansion than Yorkshire adipocytes. These finding indicate that Ossabaw adipocytes differentiate to a greater extent than Yorkshire adipocytes.;Finally, we evaluated global gene expression in subcutaneous and visceral adipose tissue of restricted and ad libitum fed Ossabaw swine by using an Affymetrix microarray. Microarray analysis revealed no differentially expressed genes between lean and obese Ossabaw swine. This result coincides with no metabolic alterations induced by obesity relating to glucose homeostasis or serum lipids.;Collectively, we have demonstrated that dietary factors influence the development of metabolic alterations in Ossabaw swine as evidenced by the induction of insulin resistance by high dietary palm oil, the attenuation of insulin resistance by the addition of n-3 fatty acids, and the lack of differentially expressed genes in the adipose tissue of obese Ossabaw swine when consuming a diet without added fat. Additionally, even in the presence of insulin resistance, there was minimal evidence of inflammation beyond the slight increase in the inflammatory CD16–CD14 + macrophages in the adipose tissue of Ossabaw swine fed a high dietary palm oil. Palmitate-induced interleukin 8 secretion by Yorkshire adipocytes, but not Ossabaw adipocytes, further supports that Ossabaw swine are resistant to obesity-linked inflammation. The ability of Ossabaw swine to expand adipose tissue may afford protection against the induction of inflammation by diet-induced obesity. Further research into the role of adipose expansion and protection against inflammation is warranted. (Abstract shortened by UMI.).