Current Models of Fatty Liver Disease; New Insights, Therapeutic Targets and Interventions

SMN Depleted Mice Offer a Robust and Rapid Onset Model of Nonalcoholic Fatty Liver Disease

“…8 This is in part due to the complex nature of NAFLD pathogenesis, which may involve multiple organ systems, including peripheral adipose tissue, the gut, and potentially other metabolic organs. 6,9 Although simple steatosis appears to be a consequence of an imbalance of fatty acid input (lipogenesis, import) and output (fatty acid oxidation, export) in the liver, 10 it is currently hypothesized that "multiple hits" are required to develop NASH and more severe phenotypes. 6 Multiple mouse models of NAFLD exist and offer great insight into molecular signaling events.…”

“…For example, the Western-style diet (or fast food diet) can take as much as 6 months to lead to the development of NASH. 9 , 13 On the other hand, the methionine- and choline-deficient diet (MCD) leads to a much faster NASH phenotype (∼2–8 weeks), yet the pathogenic mechanisms lack the systemic features of the human presentation marked by metabolic syndrome. 14 , 15 Monogenic models have also found a place in the NAFLD arena.…”

“… 6 , 16 Moreover, single gene models are considered a reductionist approach to the pathogenesis of NAFLD. 9 Although these represent only a few examples of all available models, very few, if any, offer a rapid onset of NAFLD/NASH, which would allow for efficient identification of molecular targets and testing of therapeutic strategies.…”