Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis

  title={Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis},
  author={Kristiaan Wouters and Patrick J. J. van Gorp and Veerle Bieghs and Marion J J Gijbels and Hans J Q Duimel and Dieter L{\"u}tjohann and Anja Kerksiek and Roger van Kruchten and Nobuyo Maeda and Bart Staels and Marc van van Bilsen and Ronit Shiri-Sverdlov and Marten H. Hofker},
Nonalcoholic steatohepatitis (NASH) involves liver lipid accumulation (steatosis) combined with hepatic inflammation. The transition towards hepatic inflammation represents a key step in pathogenesis, because it will set the stage for further liver damage, culminating in hepatic fibrosis, cirrhosis, and liver cancer. The actual risk factors that drive hepatic inflammation during the progression to NASH remain largely unknown. The role of steatosis and dietary cholesterol in the etiology of diet… 

Dietary cholesterol exacerbates hepatic steatosis and inflammation in obese LDL receptor-deficient mice

Dietary cholesterol appears to confer a second “hit” that results in a distinct hepatic phenotype characterized by increased inflammation and oxidative stress, and LDLR−/− mice fed diabetogenic diets may be useful models for studying human NASH.

Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic syndrome and non-alcoholic steatohepatitis with liver fibrosis

A murine NASH model with distinct hepatic steatosis, inflammation and fibrosis, without renal pathology is described, which is well suitable for NASH research.

Impact of dietary fat on the development of non-alcoholic fatty liver disease in Ldlr−/− mice

A mouse model of NASH is developed and DHA was equal or superior to EPA at attenuating WD-induced dyslipidemia and hepatic injury, inflammation, oxidative stress and fibrosis, providing a molecular and metabolic basis for understanding the strengths and weaknesses of using dietary n-3 PUFA to prevent NASH in human subjects.

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Western diet in ApoE-LDLR double-deficient mouse model of atherosclerosis leads to hepatic steatosis, fibrosis, and tumorigenesis

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Induction of Non-Alcoholic Fatty Liver Disease in Mice

The progress or development of NAFLD in each mouse model depends on the method and period of induction, which should be accordingly considered to the research objectives to achieve a precise and accurate result, and effectiveness of the outcome.

Ces3/TGH Deficiency Attenuates Steatohepatitis

It is found that mice lacking triacylglycerol hydrolase (TGH) are protected from high-fat diet (HFD) - induced hepatic steatosis via decreased lipogenesis, increased fatty acid oxidation and improved hepatic insulin sensitivity, and that TGH deficiency attenuated both simple hepatic Steatosis and irreversible NASH.

Is Western Diet-Induced Nonalcoholic Steatohepatitis in Ldlr-/- Mice Reversible?

Low-fat low-cholesterol diets promote reversal of many, but not all, features associated with WD-induced NASH and fibrosis in Ldlr-/- mice, establishing a temporal link between plasma markers of inflammation and hepatic PUFA and Fibrosis.

Menhaden oil decreases high-fat diet-induced markers of hepatic damage, steatosis, inflammation, and fibrosis in obese Ldlr-/- mice.

In conclusion, MO [C20-22 (n-3) PUFA at 2% of energy] decreases many, but not all, HF diet-induced markers of fatty liver disease in mice.

Chronic inflammation aggravates metabolic disorders of hepatic fatty acids in high-fat diet-induced obese mice

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Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis

Results from this mouse model would suggest accumulation of triglycerides may be a protective mechanism to prevent progressive liver damage in NAFLD.

Mouse models in non‐alcoholic fatty liver disease and steatohepatitis research

The physiological processes that underlie the pathogenesis and progression of NAFLD as a framework are reviewed, the strengths and weaknesses of established models are highlighted and the key findings that have furthered the understanding of disease pathogenesis are described.

Lipid‐induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet

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Polymorphism in microsomal triglyceride transfer protein: A link between liver disease and atherogenic postprandial lipid profile in NASH?

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A unique animal model mimicking some of the physiopathological features of nonalcoholic fatty liver disease using high-cholesterol-fed rabbits is established and may be useful for elucidating the mechanism of NAFLD related mainly to hyperlipidemia.

Abnormal lipid and glucose metabolism in obesity: implications for nonalcoholic fatty liver disease.

Cytokines secreted by white adipose tissue, adipokines, have emerged as key players in glucose and fat metabolism previously thought controlled largely by insulin, and may aid in further understanding of the pathophysiology and treatment of nonalcoholic fatty liver disease.

Foam cells generated by a combination of hyperglycemia and hyperlipemia in rats

Results suggest that the origin of these foam cells can be attributed to lipid‐laden macrophages, and the generation of foam cells in the hyperglycemia‐hyperlipidemia supervening rat model presented in the present study might be a useful tool for investigations of the pathogenesis of foam Cells.