The expression signatures in liver and adipose tissue from obese Göttingen Minipigs reveal a predisposition for healthy fat accumulation

Abstract

Abstract Background Model animals are valuable resources for dissecting basic aspects of the regulation of obesity and metabolism. The translatability of results relies on understanding comparative aspects of molecular pathophysiology. Several studies have shown that despite the presence of overt obesity and dyslipidemia in the pig key human pathological hepatic findings such as hepatocellular ballooning and abundant steatosis are lacking in the model. Objectives The aim of this study was to elucidate why these histopathological characteristics did not occur in a high fat, fructose and cholesterol (FFC) diet-induced obese Göttingen Minipig model. Methods High-throughput expression profiling of more than 90 metabolically relevant genes was performed in liver, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of male minipigs diet fed: standard chow (SD, n = 7); FFC diet (n = 14); FFC diet in streptozotocin-induced diabetic pigs (FFCDIA, n = 8). Moreover, histopathological assessment of SAT and VAT was performed. Results 12, 4 and 1 genes were highly significantly differentially expressed in liver, SAT and VAT when comparing the FFC and SD groups whereas the corresponding numbers were 15, 2, and 1 when comparing the FFCDIA and SD groups. Although the minipigs in both FFC groups developed sever obesity and dyslipidemia, the insulin-signaling pathways were not affected. Notably, four genes involved in lipid acquisition and removal, were highly deregulated in the liver: PPARG, LPL, CD36 and FABP4. These genes have been reported to play a major role in promoting hepatic steatosis in rodents and humans. Since very little macrophage-associated pro-inflammatory response was detected in the adipose tissues the expansion appears to have no adverse impact on adipose tissue metabolism. Conclusion The study shows that morbidly obese Göttingen Minipigs are protected against many of the metabolic and hepatic abnormalities associated with obesity due to a remarkable ability to expand the adipose compartments to accommodate excess calories.