Cholic acid supplementation accelerates the progression of nonalcoholic fatty liver disease to the procarcinogenic state in mice fed a high-fat and high-cholesterol diet

Author(s):  
Hee Jeong Chun ◽  
Yeon Joo Shim ◽  
Young Hye Kwon
Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 604
Author(s):  
Victoria Svop Jensen ◽  
Christian Fledelius ◽  
Erik Max Wulff ◽  
Jens Lykkesfeldt ◽  
Henning Hvid

The use of translationally relevant animal models is essential, also within the field of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Compared to frequently used mouse and rat models, the hamster may provide a higher degree of physiological similarity to humans in terms of lipid profile and lipoprotein metabolism. However, the effects in hamsters after long-term exposure to a NASH diet are not known. Male Syrian hamsters were fed either a high-fat, high-fructose, high-cholesterol diet (NASH diet) or control diets for up to 12 months. Plasma parameters were assessed at two weeks, one, four, eight and 12 months and liver histopathology and biochemistry was characterized after four, eight and 12 months on the experimental diets. After two weeks, hamsters on NASH diet had developed marked dyslipidemia, which persisted for the remainder of the study. Hepatic steatosis was present in NASH-fed hamsters after four months, and hepatic stellate cell activation and fibrosis was observed within four to eight months, respectively, in agreement with progression towards NASH. In summary, we demonstrate that hamsters rapidly develop dyslipidemia when fed a high-fat, high-fructose, high-cholesterol diet. Moreover, within four to eight months, the NASH-diet induced hepatic changes with resemblance to human NAFLD.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Ting Chen ◽  
Fahu Yuan ◽  
Hualin Wang ◽  
Yu Tian ◽  
Lei He ◽  
...  

Recent experimental studies and clinical trials have shown that hepatic cholesterol metabolic disorders are closely related to the development of nonalcoholic fatty liver disease (NAFLD). The main goal of this study was to investigate the efficacy of the perilla oil rich in alpha-linolenic acid (ALA) against NASH and gain a deep insight into its potential mechanisms. Rats were fed a high-fat/high-cholesterol diet (HFD) supplement with perilla oil (POH) for 16 weeks. Routine blood biochemical tests and histological staining illustrated that the perilla oil administration improved HFD-induced hyperlipidemia, reduced hepatic steatosis, and inhibited hepatic inflammatory infiltration and fibrosis. Perilla oil also increased fecal bile acid and cholesterol excretion. Hepatic RNA-Seq analysis found that the long time perilla oil supplement notably modified the gene expression involved in cholesterol metabolism. Our results implicate that, after long-term high level dietary cholesterol feeding, rat liver endogenous synthesis of cholesterol and cholesterol-rich low density lipoprotein uptake was significantly inhibited, and perilla oil did not modulate expression of genes responsible for cholesterol synthesis but did increase cholesterol removed from hepatocytes by conversion to bile acids and increased fecal cholesterol excretion.


Endocrinology ◽  
2014 ◽  
Vol 155 (12) ◽  
pp. 4697-4705 ◽  
Author(s):  
Anisha A. Gupte ◽  
Omaima M. Sabek ◽  
Daniel Fraga ◽  
Laurie J. Minze ◽  
Satoru K. Nishimoto ◽  
...  

Nonalcoholic fatty liver disease, particularly its more aggressive form, nonalcoholic steatohepatitis (NASH), is associated with hepatic insulin resistance. Osteocalcin, a protein secreted by osteoblast cells in bone, has recently emerged as an important metabolic regulator with insulin-sensitizing properties. In humans, osteocalcin levels are inversely associated with liver disease. We thus hypothesized that osteocalcin may attenuate NASH and examined the effects of osteocalcin treatment in middle-aged (12-mo-old) male Ldlr−/− mice, which were fed a Western-style high-fat, high-cholesterol diet for 12 weeks to induce metabolic syndrome and NASH. Mice were treated with osteocalcin (4.5 ng/h) or vehicle for the diet duration. Osteocalcin treatment not only protected against Western-style high-fat, high-cholesterol diet-induced insulin resistance but substantially reduced multiple NASH components, including steatosis, ballooning degeneration, and fibrosis, with an overall reduction in nonalcoholic fatty liver disease activity scores. Further, osteocalcin robustly reduced expression of proinflammatory and profibrotic genes (Cd68, Mcp1, Spp1, and Col1a2) in liver and suppressed inflammatory gene expression in white adipose tissue. In conclusion, these results suggest osteocalcin inhibits NASH development by targeting inflammatory and fibrotic processes.


2020 ◽  
Vol 11 (7) ◽  
pp. 6115-6127
Author(s):  
Gang Wang ◽  
Ting Jiao ◽  
Yue Xu ◽  
Daozheng Li ◽  
Qian Si ◽  
...  

B. adolescentis and L. rhamnosus alleviate non-alcoholic fatty liver disease induced by a high-fat, high-cholesterol diet through modulation on different gut microbiota-dependent pathways. The SCFAs are important participants.


2019 ◽  
Vol 68 (2) ◽  
pp. 147-158 ◽  
Author(s):  
Ginga Komatsu ◽  
Toru Nonomura ◽  
Mai Sasaki ◽  
Yuki Ishida ◽  
Satoko Arai ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hyo Jung An ◽  
Yoon Jung Lee ◽  
Chong Pyo Choe ◽  
Hyun-Kyung Cho ◽  
Dae Hyun Song

AbstractThe mechanism of nonalcoholic fatty liver disease (NAFLD) has not been completely revealed. In this study, we investigated the association of liver histological changes and long noncoding RNAs (lncRNAs) in the NAFLD zebrafish model. Forty zebrafish were fed a high-cholesterol diet (1.5 g per day) for 8 weeks. We measured fatty liver changes in the zebrafish liver using oil red O staining and divided them into two groups based on high and low scores. We pooled each group of zebrafish livers and identified lncRNAs, miRNAs, and mRNAs using Next-generation sequencing. Human homologs of lncRNAs were identified using ZFLNC, Ensembl, and NONCODE. We found several significant genes, including 32 lncRNAs, 5 miRNA genes, and 8 protein-coding genes, that were associated with liver metabolism and NAFLD-related functions in zebrafish. In particular, eight conserved human homologs of lncRNAs were found. We discovered the human homologs of eight lncRNA candidates from fatty liver zebrafish for the first time. The spectrum of biological mechanisms by which lncRNAs mediate their functional roles in NAFLD in a high cholesterol diet adult zebrafish model remains to be uncovered.


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