Add Copyright: © 2026 Machado et Al

Copyright%3A-%C2%A9-2026-Machado-et-Al.md

@@ -0,0 +1,7 @@
+<br>This article has been corrected. Non-alcoholic steatohepatitis (NASH), the potentially progressive form of nonalcoholic fatty liver disease (NAFLD), is the pandemic liver disease of our time. Although there are several animal models of NASH, consensus regarding the optimal model is lacking. We aimed to compare features of NASH in the two most widely-used mouse models: methionine-choline deficient (MCD) diet and Western diet. Mice were fed standard chow, MCD diet for 8 weeks, or Western diet (45% energy from fat, predominantly saturated fat, with 0.2% cholesterol, plus drinking water supplemented with fructose and glucose) for 16 weeks. Liver pathology and metabolic profile were compared. The metabolic profile associated with human NASH was better mimicked by Western diet. Although hepatic steatosis (i.e., triglyceride accumulation) was also more severe, liver non-esterified [fatty acid](https://www.youtube.com/results?search_query=fatty%20acid) content was lower than in the MCD diet group. NASH was also less severe and less reproducible in the Western diet model, as evidenced by less liver cell death/apoptosis, inflammation, ductular reaction, and fibrosis.<br>
+
+<br>Various mechanisms implicated in human NASH pathogenesis/progression were also less robust in the Western diet model, including oxidative stress, ER stress, autophagy deregulation, and hedgehog pathway activation. Feeding mice a Western diet models metabolic perturbations that are common in humans with mild NASH, whereas administration of a MCD diet better models the pathobiological mechanisms that cause human NAFLD to progress to advanced NASH. Citation: Machado MV, Michelotti GA, Xie G, de Almeida TP, Boursier J, Bohnic B, et al. 2015) Mouse Models of Diet-Induced Nonalcoholic Steatohepatitis Reproduce the Heterogeneity of the Human Disease. PLoS ONE 10(5): e0127991. Copyright: © 2015 Machado et al. Data Availability: All [relevant data](https://www.savethestudent.org/?s=relevant%20data) are within the paper and its Supporting Information files. Funding: This research is supported by NIH DK0077794 and DK053792 (Diehl AM), and Duke Endowment: The Florence McAlister Professorship (Diehl AM). MVM received a PhD grant from Fundação para a Ciência e Tecnologia, FCT, Portugal.<br>
+
+<br>The funders had no role in study design, dara collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Although the majority of patients will have a benign evolution, up to 25% develop potentially progressive liver damage, dubbed nonalcoholic steatohepatitis (NASH). Though much has been learned about NAFLD since its first descriptions thirty years ago, there are still huge gaps in knowledge regarding its pathogenesis, prognosis, prevention, and treatment. Studying human NAFLD is hampered by the fact that it encompasses a spectrum of conditions difficult to differentiate non-invasively. Also, NAFLD is a very slowly progressive disease, which hinders prospective observational studies. Given these challenges, animal models that mimic human pathology are a necessity. The perfect animal model would develop NAFLD in the context of key risk factors for the human condition (i.e., obesity and  [Medic GLP Supplement](https://rentry.co/47026-glp-weight-loss-a-revolutionary-approach-to-obesity-management) the metabolic syndrome, MS), eventually manifest all histological features of NASH, progress to advanced liver fibrosis, and be susceptible to hepatocellular carcinoma.<br>
+
+<br>Importantly, the ideal NASH model should require little time and expense to develop/maintain, and be highly reproducible. There are several diet-induced models of NAFLD/NASH in small animals. Mice are generally preferred due to their short lifespan and the ease of genetically manipulating putative pathogenic/protective pathways. The most widely used diet to induce NAFLD/NASH is the methionine-choline deficient (MCD) diet. High-fat diet is another highly studied approach to develop NAFLD. The heterogeneity of such diets makes it difficult to compare studies from different research groups. More recently, a modified high-fat diet has been used to model of NAFLD/NASH. The Western diet has the advantage of inducing obesity and  [Medic GLP Supplement](https://lab.dutt.ch/catharinegurne/evonne2018/wiki/Retatrutide+-+Revolutionary+recently+Developed+GLP+Agonist+-+Literature+Review.-) the MS in mice, although requiring long-term administration. In this study, we performed a head-to-head comparison of the MCD and Western diets after controlling for multiple variables that impact metabolism and NAFLD pathogenesis: mouse genetic background, age, gender, and inter-animal facility-related differences in light-dark cycling and indigenous microbial flora.<br>