Early hepatic proteomic signatures reveal metabolic changes in high fat induced obesity in rats.

The prevalence of diet-related obesity is increasing dramatically worldwide, making it important to understand the associated metabolic alterations in the liver. It is well known that obesity is a multifactorial condition that is the result of complex integration between many gene expression and dietary factors. Obesity alone or in conjunction with other chronic diseases such as diabetes, insulin resistance causes many health problems and is considered a major risk factor for developing nonalcoholic steatohepatitis and cirrhosis. In this study, we aimed to understand the molecular mechanisms underlying early hepatic changes in the pathophysiology of high-fat diet-induced abdominal obesity in rats. Hepatic protein profiles of normal and high-fat diet-induced obesity for 24weeks were analyzed using differential two-dimensional gel electrophoresis(DIGE) and protein identification by mass spectrometry. 52proteins were identified by MALDI-TOF and computer-assisted DIGE image software analysis showed that 18 major proteins were significantly differentially expressed between comparable groups, with 2.0-4.0-fold change/more(p<0.01). These proteins are regulated in response to a high-fat diet and differentially expressed proteins are involved in key metabolic pathways such as lipid metabolism, energy metabolism, detoxification, urea cycle and hepatic calcium homeostasis. In addition, western blot and immunohistochemistry of liver-specific-arginase-1(Arg-1) showed significant increased expression in the liver of high-fat-fed rats(p<0.01). Further, Arg-1 expression was correlated with NASH patients with obesity-related fibrosis (F0-F4). To conclude that high fat content may affect changes in liver pathways and may be a therapeutic target for obesity-related liver disease. Arg-1 expressions may be a potential pathological marker for assessing the progression of the disease.