Life sciences (1973), 2021-07, Vol.276, p.119403-119403, Article 119403
2021
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- Autor(en) / Beteiligte
- Titel
- A rapid juvenile murine model of nonalcoholic steatohepatitis (NASH): Chronic intermittent hypoxia exacerbates Western diet-induced NASH
- Ist Teil von
- Life sciences (1973), 2021-07, Vol.276, p.119403-119403, Article 119403
- Ort / Verlag
- Netherlands: Elsevier Inc
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Many dietary NASH models require a long duration to establish (4–6 months). Chronic intermittent hypoxia (CIH), a cardinal hallmark of obstructive sleep apnea (OSA), may accelerate the progression of pediatric nonalcoholic fatty liver disease (NAFLD). However, diet-induced obese (DIO) mice exposed to CIH have not been perceived as a fast or reliable tool in NASH research. This study was designed to establish a rapid juvenile murine NASH model, and determine whether the combination of CIH and a western-style diet (hypercaloric fatty diet plus high fructose) can fully display key pathologic features of NASH. C57BL/6 N mice (3 weeks old) fed a control diet or western diet (WD) were exposed to CIH (9% nadir of inspired oxygen levels) or room air for 6 and 12 weeks. The Control/CIH group mainly exhibited hyperinsulinemia and insulin resistance (IR). In contrast, mice fed a WD developed weight gain after 3 weeks, microvesicular steatosis in 6 weeks, and indices of metabolic disorders at 12 weeks. Furthermore, CIH exposure accelerated WD- induced macromicrovesicular steatosis (liver triglycerides and de novo lipogenesis), liver injury (ballooned hepatocytes and liver enzymes), lobular/portal inflammation (inflammatory cytokines and macrophage recruitment), and fibrogenesis (hydroxyproline content and TGF-β protein). Notably, only the WD/CIH group exhibited elevated hepatic MDA content, protein levels of NOX4, α-SMA and collagen I, as well as reduced Nrf2 and HO-1 protein expression. WD/CIH treatment rapidly mimics the histological characteristics of pediatric NASH with metabolic dysfunction and fibrosis, representing an appropriate experimental model for NASH research.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0024-3205eISSN: 1879-0631DOI: 10.1016/j.lfs.2021.119403Titel-ID: cdi_proquest_miscellaneous_2507670141
- Format
- –
- Schlagworte
- Animal models, Animals, Animals, Newborn, Apnea, Body weight gain, Chronic intermittent hypoxia, Collagen (type I), Cytokines, Diet, Diet, Western - adverse effects, Exposure, Fatty liver, Fibrosis, Heme oxygenase (decyclizing), Hepatocytes, Hydroxyproline, Hyperinsulinemia, Hypoxia, Hypoxia - physiopathology, Inflammation, Inflammation - etiology, Inflammation - metabolism, Inflammation - pathology, Insulin, Insulin Resistance, Juvenile murine model, Lipogenesis, Liver, Liver diseases, Macrophages, Male, Metabolic disorders, Metabolism, Mice, Mice, Inbred C57BL, NAFLD, NASH, Non-alcoholic Fatty Liver Disease - etiology, Non-alcoholic Fatty Liver Disease - metabolism, Non-alcoholic Fatty Liver Disease - pathology, NOX4 protein, Oxidative Stress, Pediatrics, Proteins, Sleep, Sleep disorders, Steatosis, Triglycerides, Western diet