Analysis of differentially expressed serum proteins during development of obesity

Abstract

Obesity is a complex and chronic disease that is associated with many complications including type 2 diabetes (T2D). However, the mechanism leading to these events is unclear. To determine the role played by obesity in the development of T2D, it was purposed to examine serum protein profiles of diet-induced obese Wistar rats. These protein(s) will be used as potential biomarkers for early detection, diagnosis, as target for drug discovery and hopefully treatment of obesity and obesity-induced disorders. An animal model of obesity-induced T2D was established by feeding male Wistar rats a diet with a high fat content for 44 weeks. Weight changes and food intake were monitored weekly during the diet phase. Fasting blood glucose levels were measured while blood was collected for serumpreparation every second week for the first eight weeks; using these parameters, a model for the identification of diet-induced obese rats was established. Serum protein profiles were then compared between the two groups using 2D-PAGE analysis coupled to MALDI-MS at termination of the study. Several proteins showed differences in their expression when compared between the low fat (LF) and high fat (HF) groups. However, only proteins that showed expression that was either two fold low or high between the two groups were considered to be differentially expressed.

High fat fed rats weighed significantly heavier starting at the fourth week on diet and throughout the study, their glucose homeostasis and serum protein expression was altered. Three protein spots were identified as dysregulated in the HF group, where Apolipoprotein-AIV was found to have been up-regulated whereas C-reactive protein and Fetuin-A were down-regulated. These proteins might help in the understanding of the mechanism(s)that underlie the pathogenesis of obesity and its related disorders. However, further studies are required to determine the relationship between these proteins, obesity development and its comorbidities.