Freshwater clam extract reduces liver injury by lowering cholesterol accumulation, improving dysregulated cholesterol synthesis and alleviating inflammation in high-fat, high-cholesterol and cholic acid diet-induced steatohepatitis in mice

2018 ◽  
Vol 9 (9) ◽  
pp. 4876-4887 ◽  
Author(s):  
Hsien-Tsung Yao ◽  
Pei-Feng Lee ◽  
Chong-Kuei Lii ◽  
Yun-Ta Liu ◽  
Szu-Han Chen
Keyword(s):  
Liver Injury ◽  
Cholic Acid ◽  
Cholesterol Synthesis ◽  
Corbicula Fluminea ◽  
High Cholesterol ◽  
High Fat ◽  
Cholesterol Accumulation ◽  
Freshwater Clam ◽  
Acid Diet ◽  
Protective Food

Freshwater clam (Corbicula fluminea) is a traditional liver-protective food in Asia.

scholarly journals A Diterpenoid, 14-Deoxy-11, 12-Didehydroandrographolide, in Andrographis paniculata Reduces Steatohepatitis and Liver Injury in Mice Fed a High-Fat and High-Cholesterol Diet

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 523 ◽  
Author(s):  
Yun-Ta Liu ◽  
Haw-Wen Chen ◽  
Chong-Kuei Lii ◽  
Jia-Hua Jhuang ◽  
Chin-Shiu Huang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Caspase 3 ◽  
Andrographis Paniculata ◽  
Receptor Protein ◽  
Heme Oxygenase 1 ◽  
Nuclear Factor ◽  
High Cholesterol ◽  
High Fat ◽  
Cholesterol Accumulation ◽  
Anti Inflammatory

14-Deoxy-11,12-didehydroandrographolide (deAND), a diterpenoid in Andrographis paniculata (Burm. f.) Nees, acts as a bioactive phytonutrient that can treat many diseases. To investigate the protective effects of deAND on reducing fatty liver disease, male mice were fed a high-fat and high-cholesterol (HFHC) diet without or with 0.05% and 0.1% deAND supplementation. Cholesterol accumulation, antioxidant, and anti-inflammatory activities in liver and liver injury were evaluated after deAND treatment. The results show that deAND treatment for seven weeks reduced plasma alanine aminotransferase activity and lowered hepatic cholesterol accumulation, tumor nuclear factor-α, and histological lesions. The 0.1% deAND treatment reduced HFHC diet-induced apoptosis by lowering the caspase 3/pro-caspase 3 ratio. After 11 weeks of deAND treatment, increased NOD-like receptor protein 3 (NLRP3), capase-1, and interleukin-1β protein levels in liver were suppressed by deAND treatment. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression, heme oxygenase-1 protein expression, and the activities of glutathione peroxidase and glutathione reductase were increased in mice fed the HFHC diet. However, those activities of antioxidant enzymes or proteins were also upregulated by 0.1% deAND treatment. Furthermore, deAND treatment tended to lower hepatic lipid peroxides. Finally, deAND treatment reversed the depletion of hepatic glutamate level induced by the HFHC diet. These results indicate that deAND may ameliorate HFHC diet-induced steatohepatitis and liver injury by increasing antioxidant and anti-inflammatory activities.

scholarly journals Benzyl Isothiocyanate Reduces High-Fat/High-Cholesterol/Cholic Acid Diet-Induced Non-Alcoholic Steatohepatitis by Inhibiting the Activation of NLRP3 Inflammasome (P06-084-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Li-Li Ko ◽  
Haw-wen Chen ◽  
Chong-Kuei Lii
Keyword(s):  
Total Cholesterol ◽  
Cholic Acid ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
High Cholesterol ◽  
High Fat ◽  
Benzyl Isothiocyanate ◽  
Alcoholic Steatohepatitis ◽  
Caspase 1 ◽  
Acid Diet

Abstract Objectives Non-alcoholic steatohepatitis (NASH) is one kind of fatty liver disease, which is associated with obesity. Benzyl isothiocyanate (BITC), an organosulfur compound enriched in cruciferous vegetables, shows anti-inflammatory, antioxidant, and anti-tumor activities. This study examined whether BITC protects against high-fat/high-cholesterol/cholic acid diet-induced NASH and the underlying mechanisms involved. Methods Male C57BL/6 J mice were randomly assigned into three groups: normal diet (ND), high-fat/high-cholesterol/cholic acid diet (HFCCD), or HFCCD supplemented with 0.1% BITC. After a 9-weeks feeding, liver tissues and blood samples were collected for analysis. Results Compared with mice fed with ND, the liver weight and the contents of serum GOP, GPT, and total cholesterol as well as hepatic triglycerides and total cholesterol were significantly increased in mice fed with HFCCD (p < 0.05). HFCCD-induced increases in serum GPT and hepatic triglyceride were significantly decreased by BITC (p < 0.05). Histological examination revealed that macrophage infiltration, fibrosis, and the formation of crown-like structure were induced in mice fed with HFCCD, and these inductions were attenuated by BITC. Increases in the expression of NLRP3 mRNA and protein and caspase 1 and IL-1β mRNA as well as the cleaved caspase 1 (p20) and IL-1β (p17) proteins in the liver as well as serum IL-1β concentration were evidenced in HFCCD-fed mice. In the presence of BITC, HFCCD-induced hepatic NLRP3, caspase 1, and IL-1β expression was mitigated. Conclusions These findings suggest that BITC possesses potent anti-steatohepatitis activity, and this protection is likely to be associated with the inhibition of NLRP3 inflammasome activation. Funding Sources This study was supported by the Minister of Science and Technology, Taiwan.

Estrogen deficiency worsens steatohepatitis in mice fed high-fat and high-cholesterol diet

2011 ◽  
Vol 301 (6) ◽  
pp. G1031-G1043 ◽  
Author(s):  
Yoshihiro Kamada ◽  
Shinichi Kiso ◽  
Yuichi Yoshida ◽  
Norihiro Chatani ◽  
Takashi Kizu ◽  
...  
Keyword(s):  
Risk Factor ◽  
Liver Injury ◽  
Postmenopausal Women ◽  
Serum Cholesterol ◽  
Estrogen Deficiency ◽  
Macrophage Infiltration ◽  
High Cholesterol ◽  
High Fat ◽  
Gene Expressions ◽  
Cholesterol Levels

Recent studies indicate an accelerated progression of nonalcoholic steatohepatitis (NASH) in postmenopausal women. Hypercholesterolemia, an important risk factor for NASH progression, is often observed after menopause. This study examined the effects of estrogen on NASH in ovariectomized (OVX) mice fed a high-fat and high-cholesterol (HFHC) diet. To investigate the effects of estrogen deficiency, OVX mice and sham-operated (SO) mice were fed normal chow or HFHC diet for 6 wk. Next, to investigate the effects of exogenous estrogen replenishment, OVX mice fed with HFHC diet were treated with implanted hormone release pellets (containing 17β-estradiol or placebo vehicle) for 6 wk. OVX mice on the HFHC diet showed enhanced liver injury with increased liver macrophage infiltration and elevated serum cholesterol levels compared with SO-HFHC mice. Hepatocyte monocyte chemoattractant protein-1 (MCP1) protein expression in OVX-HFHC mice was also enhanced compared with SO-HFHC mice. In addition, hepatic inflammatory gene expressions, including monocytes chemokine (C-C motif) receptor 2 (CCR2), were significantly elevated in OVX-HFHC mice. Estrogen treatment improved serum cholesterol levels, liver injury, macrophage infiltration, and inflammatory gene expressions in OVX-HFHC mice. Moreover, the elevated expression of liver CCR2 and MCP1 were decreased by estrogen treatment in OVX-HFHC mice, whereas low-density lipoprotein dose dependently enhanced CCR2 expression in THP1 monocytes. Our study demonstrated that estrogen deficiency accelerated NASH progression in OVX mice fed HFHC diet and that this effect was improved by estrogen therapy. Hypercholesterolemia in postmenopausal women would be a potential risk factor for NASH progression.

scholarly journals Effects of dietary cholesterol and fat on serum non-cholesterol sterols according to different apolipoprotein E subgroups among healthy men

2008 ◽  
Vol 100 (2) ◽  
pp. 373-379 ◽  
Author(s):  
Markku J. Nissinen ◽  
Helena Gylling ◽  
Tatu A. Miettinen
Keyword(s):  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Dietary Cholesterol ◽  
Serum Levels ◽  
High Cholesterol ◽  
High Fat ◽  
Low Fat ◽  
Apo E ◽  
The Impact ◽  
Low Cholesterol

The impact of apo E phenotypes on applicability of relative cholesterol synthesis (lathosterol:cholesterol) and absorption (ratios of cholestanol, campesterol and sitosterol to cholesterol) during diets of various cholesterol and fat content is unclear. We examined and compared with each other both relative and absolute synthesis and absorption among twenty-nine men, of whom eight, nine and twelve had apo E phenotypes 2 (2/2, 2/3, 2/4), 3 (3/3) and 4 (3/4, 4/4), respectively. Serum lipids, lipoproteins, sterols and cholesterol metabolism were examined on four subsequent diets: high-cholesterol high-fat (home diet; HD), low-cholesterol low-fat (LCLF), high-cholesterol low-fat (HCLF) and low-cholesterol high-fat (LCHF). LDL-cholesterol (LDL-C) level was about 40 % lower (P < 0·05) in apo E2 than apo E3 and E4 groups irrespective of dietary fat and cholesterol. Serum proportions of phytosterols were determined apo E-dependently on LCLF and HCLF, and those of lathosterol, cholestanol and campesterol were increased in apo E2 and E3 groups (P < 0·05 for each v. HD). Serum proportion of sitosterol reflected almost consistently apo E phenotype (r range+0·308 to+0·383; P range 0·214–0·011). Relative cholesterol synthesis and absorption reflected respective absolute values during each diet in the apo E4 group (r range+0·713 to+0·893; P < 0·05 for each), but only during HD (r+0·594; P = 0·015) in the apo E2+E3 group. The consumption of a high amount of fat did not interfere with cholesterol metabolism or serum levels of LDL-C differently in apo E phenotypes. Surrogate sterol markers of cholesterol metabolism reflected absolute ones (especially in the apo E4 group) and apo E phenotypes despite variable amounts of dietary cholesterol and fat.

Galactomannan More than Pectin Exacerbates Liver Injury in Mice Fed with High-Fat, High-Cholesterol Diet

2018 ◽  
Vol 62 (20) ◽  
pp. 1800331 ◽  
Author(s):  
Miriam G. Shtriker ◽  
Irena Peri ◽  
Elise Taieb ◽  
Abraham Nyska ◽  
Oren Tirosh ◽  
...  
Keyword(s):  
Liver Injury ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat

A Freshwater Clam (Corbicula fluminea) Extract Improves Cholesterol Metabolism in Rats Fed on a High-Cholesterol Diet

2008 ◽  
Vol 72 (10) ◽  
pp. 2566-2571 ◽  
Author(s):  
Takeshi CHIJIMATSU ◽  
Iwao TATSUGUCHI ◽  
Kazuaki ABE ◽  
Hiroaki ODA ◽  
Satoshi MOCHIZUKI
Keyword(s):  
Cholesterol Metabolism ◽  
Corbicula Fluminea ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Freshwater Clam ◽  
Clam Corbicula

scholarly journals Changes in LXRα phosphorylation promote a novel diet-induced transcriptome that alters the transition from fatty liver to steatohepatitis

2017 ◽  
Author(s):  
Natalia Becares ◽  
Matthew C Gage ◽  
Lucia Martin-Gutierrez ◽  
Elina Shrestha ◽  
Rikah Louie ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Liver Steatosis ◽  
High Cholesterol Diet ◽  
Hepatic Inflammation ◽  
High Cholesterol ◽  
High Fat ◽  
Cholesterol Accumulation ◽  
Liver Transcriptome ◽  
Fibrotic Steatohepatitis ◽  
Liver X Receptor Alpha

SUMMARYUnderstanding the transition from fatty liver (steatosis) to inflammatory and fibrotic steatohepatitis, is key to define strategies that alter its progression. Here we show that, when challenged with a high fat-high cholesterol diet, mice carrying a mutation that abolishes phosphorylation at Ser196 (S196A) in the liver X receptor alpha (LXRα) exhibit reduced hepatic inflammation and fibrosis despite displaying enhanced steatosis. This is associated with a marked protection against cholesterol accumulation. Reduced steatohepatitis in S196A mice involves unique reprogramming of the liver transcriptome in response to the diet. Remarkably, impaired LXRα phosphorylation uncovers novel diet-specific/phosphorylation-sensitive genes, whose regulation does not simply mirror ligand-induced LXR activation. Regulation of these unique, dually responsive genes, is associated with the promotion of LXR and cofactor occupancy under a cholesterol-rich diet. Therefore, Ser196-LXRα phosphorylation acts as a novel nutritional sensor that triggers a unique diet-induced transcriptome, thereby modulating metabolic, inflammatory and fibrotic responses important in the transition to steatohepatitis.

scholarly journals Linarin Enriched Extract Attenuates Liver Injury and Inflammation Induced by High-Fat High-Cholesterol Diet in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Zhen-Jie Zhuang ◽  
Chao-Wen Shan ◽  
Bo Li ◽  
Min-Xia Pang ◽  
Han Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Normal Diet ◽  
Liver Cholesterol ◽  
High Cholesterol Diet ◽  
High Dose ◽  
Mrna Levels ◽  
High Cholesterol ◽  
High Fat ◽  
Beneficial Effects ◽  
Chemotactic Protein

The aim of this study was to explore the potential beneficial effects of linarin enriched Flos Chrysanthemi extract (Lin-extract) on nonalcoholic steatohepatitis (NASH) induced by high-fat high-cholesterol (HFHC) diet in rats. SD rats received normal diet, HFHC diet, or HFHC diet plus different doses of Lin-extract. The liver content of triglyceride and total cholesterol markedly increased in HFHC diet-fed model rats while middle and high dose of Lin-extract lowered liver cholesterol significantly. The expression of stearoyl-CoA desaturase (SCD1) was upregulated by HFHC diet and further elevated by high dose Lin-extract. High dose of Lin-extract also markedly lowered the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and inhibited the activation of c-Jun N-terminal kinase (JNK) induced by HFHC in livers. The HFHC-increased mRNA levels of hepatic inflammation cytokines, including monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α(TNF-α), and chemokine (C-X-C motif) ligand 1 (CXCL1), were suppressed by Lin-extract dose-dependently. Furthermore, pathology evaluation showed that high dose Lin-extract greatly improved lobular inflammation. Our results suggest that Lin-extract could attenuate liver injury and inflammation induced by HFHC diet in rats. Its modulatory effect on lipid metabolism may partially contribute to this protective effect.

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