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Pathogenesis of fatty liver diseases (FLD) and their small animal models |
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| รหัสดีโอไอ | |
| Creator | Nadta Sukkasem |
| Title | Pathogenesis of fatty liver diseases (FLD) and their small animal models |
| Contributor | Waranya Chatuphonprasert, Kanokwan Jarukamjorn |
| Publisher | Faculty of Pharmaceutical Sciences KKU MSU UBU |
| Publication Year | 2561 |
| Journal Title | Isan Journal of Pharmaceutical Sciences |
| Journal Vol. | 14 |
| Journal No. | 2 |
| Page no. | 1-15 |
| Keyword | fatty liver disease, non-alcoholic fatty liver disease, alcoholic fatty liver disease, steatosis, small animal model |
| URL Website | https://tci-thaijo.org/index.php/IJPS |
| Website title | Isan Journal ofPharmaceutical Sciences, IJPS |
| ISSN | 19050852 |
| Abstract | Fatty liver disease (FLD), including non-alcoholic (NAFLD) and alcoholic (AFLD) fatty liver diseases, are serious health problems worldwide. Both NAFLD and AFLD have similar pathological spectra, ranging from simple hepatic steatosis to steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. Notably, NAFLD and AFLD are frequently associated with extrahepatic complications, e.g. cardiovascular disease and malignancy. NAFLD is increasingly prevalent and represents a growing challenge in terms of prevention and treatment, despite advances in this field, knowledge on the pathogenesis of NAFLD is still limited. The classical 'two-hit' hypothesis, having hepatic accumulation of lipids secondary to sedentary lifestyle, high fat diet, obesity and insulin resistance as the first hit, and sensitization of the liver to inflammation acting as the 'second hit', is now outdated. The "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such "hits" include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota, and genetic/epigenetic factors. Excessive alcohol intake can lead to AFLD through its direct action as a hepatotoxin1 as well as potentiation of other liver diseases including chronic viral hepatitis and NAFLD. Animal models of NAFLD may be divided into two broad categories; those caused by genetic mutation and those with an acquired phenotype produced by dietary or pharmacological manipulation. The genetic leptin-deficient (ob/ob) or leptin-resistant (db/db) mouse and the dietary methionine/choline-deficient model have been employed in the majority of published research. More recently, targeted gene disruption and the use of supra-nutritional diets to induce NAFLD have gained greater prominence as researchers have attempted to bridge the phenotype gap between the available models and the human disease. On the other hand, several models for experimental AFLD exist, including non-human primates, micropigs and rodents. Most researchers employ rodent models of AFLD. Knock-out mice have increased the specificity of the hypotheses that can be directly tested. Based on these models systems, several plausible hypotheses have been applied to explain the pathogenesis of NAFLD and AFLD. However, despite significant advances in our understanding of the mechanisms by development of these models, further studies are still needed in order to translate these to more understandable and specific mechanisms of these diseases to develop new treatments for either NAFLD or AFLD. |
