Kucera 2017 MiP2017
NAFLD is the most common chronic liver disease in industrially developed countries with growing worldwide prevalence. Pathogenesis of NAFLD is based on a complex interplay between genetic, intrinsic and extrinsic factors. Although much scientific effort has been devoted to this problem, the pathogenesis of this disease remains not fully understood. Nevertheless, insulin resistance is considered as the most important factor in the development of the disease. Thus, NAFLD is believed to be the hepatic manifestation of metabolic syndrome. Although there are many potentially effective pharmacological agents for treatment for NAFLD, there is no generally recommended drug used in clinical practice and the usual management of NAFLD is based mainly on lifestyle changes (dietary modification, gradual weight reduction, and increase in physical activity).
To improve understanding of intricate pathogenesis of NAFLD and for identification of novel therapeutic strategies, further research is needed. Such research requires evaluation of huge amount of human samples or samples from “ideal” animal models. These models should encompass the entire characteristic of human NAFLD (histological findings, insulin resistance and metabolic syndrome phenotype, disease progression, etc.). Genetic, nutritional and combined models are the most widely used animal models of NAFLD. Genetic models include leptin signaling deficiency (ob/ob and db/db mice), LDL receptor-deficient mice, ApoE-deficient mice or SREBP-1c transgenic mice. Methionine- and choline-deficient diet, high-fat diet, fructose-rich diet, and western diet (high-fat, high-sucrose diet) belong to commonly used nutritional models. Many genetic and nutritional models need a secondary hit (lipopolysaccharide, dietary stimulus) to trigger progression of simple liver steatosis to steatohepatitis. At the moment, there is no “ideal animal model” of NAFLD. When designing an experiment, all pros and cons of a chosen model should be taken into account and respected. Only then the experimental data may help to improve the understanding of NAFLD and its treatment.
Labels: MiParea: Exercise physiology;nutrition;life style, Pharmacology;toxicology Pathology: Other
- Dept Physiol, Fac Medicine Hradec Králové, Charles Univ, Czech Republic. - [email protected]
References and support
- Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ (2012) The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 55:2005-23.
- This work was supported by research program PROGRES Q40/02 and Inter-Cost LTC17044