Porcine Adipose Spheroids - A Suitable Tool to Analyze Obesity-Related Proteins

Obesity is a growing global problem that reduces healthy life expectancy by almost 10 years due to associated comorbidities such as type 2 diabetes, cardiovascular disease and cancer. The drugs used to date that have been tested on animal models, often act systemically and are associated with a wide range of side effects. Therefore, it would be of great interest to identify mechanisms that specifically target adipocytes. Robustly established in vitro model systems can enable high-throughput screening and significantly reduce the number of animals used. One promising approach is the use of spheroids from porcine adipose tissue. Pigs are a particularly well-suited translational model organism in obesity research due to the comparable physiology of their digestive tract and fat distribution, as well as a similar expression of adipokines and regulators of lipid metabolism (e.g. PPARG). Tissue originating from meat production can be used to isolate porcine adipose derived stem cells. These cells are archived, genetically modified using CRISPR/Cas9 or RNAi as required, and finally differentiated into 3D-Models. By using different breeds with defined metabolic phenotypes, porcine spheroids allow population-relevant differences to be mapped. Compared to human primary cells, the better documentation of nutrition and genetics enables a systematic analysis of protein-dependent effects on lipogenic and lipolytic processes, for example after knockout of ERBB or LRIG proteins.