Nonalcoholic Steatohepatitis, Animal Models, and Biomarkers: What Is New?

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological term that encompasses a spectrum of abnormalities ranging from simple triglyceride accumulation in the hepatocytes (hepatic steatosis) to hepatic steatosis with inflammation (steatohepatitis, also known as nonalcoholic steatohepatitis or NASH). NASH can also progress to cirrhosis and hepatocellular carcinoma (HCC). Steatohepatitis has been estimated to affect around 5% of the total population and 20% of those who are overweight. The mechanisms leading to NASH and its progression to cirrhosis and HCC remain unclear, but it is a condition typically associated with obesity, insulin resistance, diabetes, and hypertriglyceridemia. This point corroborates the need for animal models and molecular markers that allow us to understand the mechanisms underlying this disease. Nowadays, there are numerous mice models to study abnormal liver function such as steatosis, NASH, and hepatocellular carcinoma. The study of the established animal models has provided many clues in the pathogenesis of steatosis and steatohepatitis, although these remain incompletely understood and no mice model completely fulfills the clinical features observed in humans. In addition, there is a lack of accurate sensitive diagnostic tests that do not involve invasive procedures. Current laboratory tests include some biochemical analysis, but their utility for diagnosing NASH is still poor. For that reason, a great effort is being made toward the identification and validation of novel biomarkers to assess NASH using high-throughput analysis based on genomics, proteomics, and metabolomics. The most recent discoveries and their validation will be discussed.

Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155, and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice

“…6,23,24 It is believed that that this model is the best-established experimental model to study NASH. 25 We identified 74 miRNAs (40 up-regulated and 34 down-regulated) that were differentially expressed (p<0.05) after 12 weeks of methyl deficiency (Suppl. Fig.…”

C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients

“…Current methods use invasive technologies, such as liver biopsy, in order to differentiate simple steatosis from NASH [25]. This distinction is of great importance because NASH is considered to be a disease that can evolve to cirrhosis, whereas steatosis normally does not progress and is considered benign [25].…”

“…This distinction is of great importance because NASH is considered to be a disease that can evolve to cirrhosis, whereas steatosis normally does not progress and is considered benign [25]. A specific biomarker that can distinguish between steatosis and NASH would be of great clinical usefulness.…”

“…Our results imply that in obese patients hs-CRP may be a marker of steatosis, but not an obesity-independent marker of the more severe stage of NASH. Large-scale studies in the fields of proteomics and metabolomics are performed in the serum of patients and may, in the future, identify novel biomarkers for clinical application [25].…”

Adenovirus-36 Seropositivity Enhances Effects of Nutritional Intervention on Obesity, Bright Liver, and Insulin Resistance

“…The pathology of NAFLD [5], its impact on hepatic fibrosis [6], animal models and biomarkers [7], molecular mechanisms of lipotoxicity [8], diagnostic strategies, and associated conditions [9,10] are among the most substantial fields of clinical and translational research.…”