Modeling progressive non-alcoholic fatty liver disease in the laboratory mouse

Riordan, Jesse D.; Nadeau, Joseph H.

doi:10.1007/s00335-014-9521-3

Cited by 32 publications

(27 citation statements)

References 162 publications

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“…49 The expression of NF-jB is an important factor regulating pathogenesis of NAFLD by endoplasmic reticulum stress in the liver. 4 In this study, mice fed soybean embryos showed a decrease in TNFa and NF-jB gene expression compared to the NAFLD group. We concluded that consumption of soybean embryos has an antiinflammatory effect in the liver.…”

Section: Discussionmentioning

confidence: 54%

“…Increasing the lipid content of experimental diets triggers metabolic diseases, such as obesity, hyperinsulinemia, hypercholesterolemia, and dyslipidemia. 4,5 Mice fed a high-fat diet show significant increases in body weight gain. 5 The results of this study are in agreement with previous findings of studies on mice fed high-fat diets.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies indicate that NAFLD-related ailments affect up to 46% of the U.S. population and 20% of the world population. 1,2 In general, >60% of obesity cases and 70-90% of diabetic patients are subject to NAFLD, 3,4 whereas only 3% of the general population is subject to this disease. 5,6 As NAFLD cases increase proportionately with the growing population of obese and diabetic patients, it is a rapidly increasing health problem worldwide.…”

Section: Introductionmentioning

confidence: 99%

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Hepatoprotective Effects of Soybean Embryo by Enhancing Adiponectin-Mediated AMP-Activated Protein KinaseαPathway in High-Fat and High-Cholesterol Diet-Induced Nonalcoholic Fatty Liver Disease

HongJihye

KimSera

KimHyun-Sook

2016

Journal of Medicinal Food

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Nonalcoholic fatty liver disease (NAFLD), which is characterized by >5% deposition of triglycerides in hepatocytes, is often referred as a major risk factor for obesity, type 2 diabetes, and hypertension. We investigated the hepatoprotective effect of whole soybean embryos containing bioactive substances such as isoflavones and soyasaponins. For this study, mice were randomly allocated into four groups that were fed different diets for 10 weeks: normal diets and high-fat and high-cholesterol diets (HD), and HD with 10% or 20% soybean embryo powder (10SE-HD and 20SE-HD). Hepatic superoxide dismutase and glutathione peroxidase activity of the experimental groups increased during the period of the study (P < .05). Hepatic mRNA expressions of tumor necrosis factor α, nuclear factor (erythroid-derived 2)-like 2, and Caspase 3 were decreased when soybean embryos were increased in the mice's diets. Both of the soybean embryo-treated groups showed significantly decreased serum and liver triglyceride and total cholesterol. Adiponectin, AMP-activated protein kinase (AMPK) α, hydroxymethylglutaryl-CoA reductase, sterol regulatory element-binding protein-1c, fatty acid synthase, and apolipoprotein B mRNA expressions were decreased in the mice that were fed soybean embryos. We suggest that the regular supplementation of soybean embryos might be a useful treatment for preventing NAFLD and associated complications through upregulation of adiponectin-mediated AMPKα pathway parameters, which are implicated in antioxidant, anti-inflammatory, and lipid metabolism activities.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hepatoprotective Effects of Soybean Embryo by Enhancing Adiponectin-Mediated AMP-Activated Protein KinaseαPathway in High-Fat and High-Cholesterol Diet-Induced Nonalcoholic Fatty Liver Disease

HongJihye

KimSera

KimHyun-Sook

2016

Journal of Medicinal Food

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“…For the sake of this review, we refer to this type of dietary model as a Western-like diet since some of these diets do not appropriately reflect the correct composition of a traditional, human Western diet. As well, it is worth noting that the terminology for this type of diet ranges from Cafeteria Diet, Obesogenic Diet and High Fat Diet (HFD), so there currently is not a distinct term for this dietary model 57–59 . We will review the effects of WD mouse models used in several studies based on the levels of advancement from NAFL to NASH with hepatic fibrosis.…”

Section: Western-like Diet (Wd)mentioning

confidence: 99%

Updates on Dietary Models of Nonalcoholic Fatty Liver Disease: Current Studies and Insights

et al. 2018

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Non-alcoholic fatty liver disease (NAFLD) is a disease of increasing interest as its prevalence is on the rise. NAFLD has been linked to metabolic syndrome, which is becoming more common due to the Western diet. Since NAFLD can lead to cirrhosis and related complications including hepatocellular carcinoma, the increasing prevalence is concerning and medical therapy aimed at treating NAFLD is of great interest. Researchers studying the effects of medical therapy on NAFLD use dietary mouse models. The two main types of mouse model diets are the methionine- and choline-deficient (MCD) diet and Western-like Diet (WD). Although both induce NAFLD, the mechanisms are very different. We reviewed several studies conducted within the last 5 years that use MCD diet or WD mouse models in order to mimic this disease in a way most similar to humans. The MCD diet inconsistently induces NAFLD and fibrosis and doesn’t completely induce metabolic syndrome. Thus, the clinical significance of the MCD diet is questionable. In contrast, WD mouse models consisting of high fat, cholesterol, and a combination of high fructose corn syrup, sucrose, fructose or glucose not only lead to metabolic syndrome but also induce NAFLD with fibrosis making these choices most suitable for research.

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“…It is the most common cause of cirrhosis worldwide (Lazo & Clark, 2008) and is strongly associated with the development of diabetes, obesity, hypertension, and dyslipidemia (Browning et al ., 2004a,b). The impact of NAFLD as a cause of liver cancer is projected to expand in coming years as the rate of obesity (Riordan & Nadeau, 2014) and the aging segment of the population increase (2008).…”

Section: Introductionmentioning

confidence: 99%

Ghrelin deletion protects against age‐associated hepatic steatosis by downregulating the C/EBPα‐p300/DGAT1 pathway

et al. 2017

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SummaryNonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. NAFLD usually begins as low‐grade hepatic steatosis which further progresses in an age‐dependent manner to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma in some patients. Ghrelin is a hormone known to promote adiposity in rodents and humans, but its potential role in hepatic steatosis is unknown. We hypothesized that genetic ghrelin deletion will protect against the development of age‐related hepatic steatosis. To examine this hypothesis, we utilized ghrelin knockout (KO) mice. Although no different in young animals (3 months old), we found that at 20 months of age, ghrelin KO mice have significantly reduced hepatic steatosis compared to aged‐matched wild‐type (WT) mice. Examination of molecular pathways by which deletion of ghrelin reduces steatosis showed that the increase in expression of diacylglycerol O‐acyltransferase‐1 (DGAT1), one of the key enzymes of triglyceride (TG) synthesis, seen with age in WT mice, is not present in KO mice. This was due to the lack of activation of CCAAT/enhancer binding protein‐alpha (C/EBPα) protein and subsequent reduction of C/EBPα‐p300 complexes. These complexes were abundant in livers of old WT mice and were bound to and activated the DGAT1 promoter. However, the C/EBPα‐p300 complexes were not detected on the DGAT1 promoter in livers of old KO mice resulting in lower levels of the enzyme. In conclusion, these studies demonstrate the mechanism by which ghrelin deletion prevents age‐associated hepatic steatosis and suggest that targeting this pathway may offer therapeutic benefit for NAFLD.

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Modeling progressive non-alcoholic fatty liver disease in the laboratory mouse

Cited by 32 publications

References 162 publications

Hepatoprotective Effects of Soybean Embryo by Enhancing Adiponectin-Mediated AMP-Activated Protein KinaseαPathway in High-Fat and High-Cholesterol Diet-Induced Nonalcoholic Fatty Liver Disease

Hepatoprotective Effects of Soybean Embryo by Enhancing Adiponectin-Mediated AMP-Activated Protein KinaseαPathway in High-Fat and High-Cholesterol Diet-Induced Nonalcoholic Fatty Liver Disease

Updates on Dietary Models of Nonalcoholic Fatty Liver Disease: Current Studies and Insights

Ghrelin deletion protects against age‐associated hepatic steatosis by downregulating the C/EBPα‐p300/DGAT1 pathway

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