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

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.

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Association of Serum Cholesterol and Triglyceride Levels with Agitation and Cognitive Function in a Geropsychiatry Unit

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/089198879600900201 ◽

1996 ◽

Vol 9 (2) ◽

pp. 53-56 ◽

Cited By ~ 9

Author(s):

Claudia A. Orengo ◽

Mark E. Kunik ◽

Victor A. Molinari ◽

Thomas A. Teasdale ◽

Richard H. Workman ◽

...

Keyword(s):

Cognitive Function ◽

Serum Cholesterol ◽

Serum Triglyceride ◽

Correlation Coefficients ◽

Significant Negative Correlation ◽

High Cholesterol ◽

Cholesterol Levels ◽

Elderly Inpatients ◽

Comprehensive Evaluations ◽

Relationship Of

Several studies have reported an association between aggression and cholesterol levels. The purpose of this study was to investigate the relationship of serum cholesterol and triglyceride levels with aggression and cognitive function in elderly inpatients. One hundred ten patients consecutively admitted to the Geriatric Psychiatry inpatient unit at Houston's Veterans Affairs Hospital received comprehensive evaluations by a multidisciplinary team. Fasting serum cholesterol and triglyceride levels were obtained within 3 days of admission. In addition, two geriatric psychiatrists administered the Mini-Mental State Examination (MMSE) and the Cohen-Mansfield Agitation Inventory (CMAI). Correlation coefficients were calculated between lipid levels, CMAI total and subscale scores, and MMSE scores. Multiple linear-regression analyses were done to further investigate the relation between lipid concentrations and various confounders. We found no significant correlation between serum triglyceride levels and MMSE, CMAI total, and CMAI factor scores. In addition, we found a significant positive correlation between serum cholesterol levels and physical nonaggressive behavior, and a significant negative correlation between serum cholesterol levels and MMSE scores. We found no relationship between aggressive behavior and serum cholesterol or triglyceride levels. However, an association between high cholesterol levels and agitation exists, which may be mediated by the association between high cholesterol levels and impaired cognition.

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Effects of Soybean. Cheonggukjang and Doenjang on Serum Cholesterol Level and Weight Reduction in Rats Fed a High-Fat/High-Cholesterol Diet

Korean Journal of Food Preservation ◽

10.11002/kjfp.2011.18.2.226 ◽

2011 ◽

Vol 18 (2) ◽

pp. 226-235 ◽

Cited By ~ 10

Author(s):

Jae-Joon Lee ◽

Ah-Ra Kim ◽

Hwan Lee ◽

Cheol-Ho Kim ◽

Hae-Choon Chang ◽

...

Keyword(s):

Cholesterol Level ◽

Serum Cholesterol ◽

Weight Reduction ◽

Serum Cholesterol Level ◽

High Cholesterol Diet ◽

Cholesterol Diet ◽

High Cholesterol ◽

High Fat

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Anti-hypercholesterolemic effect of Zingiber montanum extract

F1000Research ◽

10.12688/f1000research.16417.2 ◽

2019 ◽

Vol 7 ◽

pp. 1798

Author(s):

Swandari Paramita ◽

Meiliati Aminyoto ◽

Sjarif Ismail ◽

Enos Tangke Arung

Keyword(s):

Total Cholesterol ◽

Plant Extracts ◽

High Fat Diet ◽

High Cholesterol ◽

High Fat ◽

Group 4 ◽

Cholesterol Levels ◽

Group 6 ◽

Diet Control ◽

Group 2

Background: High cholesterol levels (hypercholesterolemia) has been recognized to cause various disease, most notably the cardiovascular disease. Unfortunately, most anti-hypercholesterolemic drugs deliver several side effects for patients, by which medicinal plants have begun to attract attention for treating hypercholesterolemia. Among others, Zingiber montanum (J.König) Link ex A.Dietr. has traditionally been taken for treating health problems caused by high cholesterol levels. Hence, this work aimed at investigating anti-hypercholesterolemic effects offered by the plant. Methods: This study was conducted on 30 male Wistar rats. During experiments, the subjects were divided into 6 groups (n=5), i.e. no treatment (Group 1, control); high-fat diet (Group 2, control); high-fat diet with simvastatin (Group 3); high-fat diet with plant extracts (Group 4-6 with 100, 200, and 400 mg/kg BW, respectively). After 4 weeks of treatments, blood samples were collected from each group. Then, plasma concentrations of triglycerides, total cholesterol, high density lipoproteins (HDL), and low density lipoproteins (LDL) were measured. Results: There were significant differences in total cholesterol (p=0.000), LDL (p=0.000) and triglycerides (p=0.001) for Groups 4-6 (high-fat diet treated with different plant extract doses) in comparison with Group 2 (high-fat diet, control). Meanwhile, there were no significant differences in HDL levels (p=0.830) between Group 2 (high-fat diet, control) and other groups. The results also showed significant differences in total cholesterol and LDL for subjects treated with plant extracts (Group 4, 100 mg/kg BW, p=0.000; Group 5, 200 mg/kg BW, p=0.000; Group 6, 400 mg/kg BW, p=0.000) compared to Group 2 (high-fat diet, control). Then, treatments with 400 mg/kg BW (Group 6) discovered significant reductions in total cholesterol, LDL, and triglycerides (p=0.030). Conclusion: Therefore, Z. montanum has been discovered to deliver anti-hypercholesterolemic effects to experimental subjects, making it potential to act as a natural source of anti-hypercholesterolemic agents.

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

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201800331 ◽

2018 ◽

Vol 62 (20) ◽

pp. 1800331 ◽

Cited By ~ 2

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

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Pharmacological activation of LXR in utero directly influences ABC transporter expression and function in mice but does not affect adult cholesterol metabolism

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90597.2008 ◽

2008 ◽

Vol 295 (6) ◽

pp. E1341-E1348 ◽

Cited By ~ 12

Author(s):

E. M. E. van Straten ◽

N. C. A. Huijkman ◽

J. F. W. Baller ◽

F. Kuipers ◽

T. Plösch

Keyword(s):

Fetal Development ◽

Cholesterol Metabolism ◽

In Utero ◽

Cholesterol Homeostasis ◽

High Cholesterol Diet ◽

Cholesterol Diet ◽

High Cholesterol ◽

High Fat ◽

Hepatic Expression ◽

Cholesterol Levels

Cholesterol is critical for several cellular functions and essential for normal fetal development. Therefore, its metabolism is tightly controlled during all life stages. The liver X receptors-α (LXRα; NR1H3) and -β (LXRβ; NR1H2) are nuclear receptors that are of key relevance in coordinating cholesterol and fatty acid metabolism. The aim of this study was to elucidate whether fetal cholesterol metabolism can be influenced in utero via pharmacological activation of LXR and whether this would have long-term effects on cholesterol homeostasis. Administration of the LXR agonist T0901317 to pregnant mice via their diet (0.015% wt/wt) led to induced fetal hepatic expression levels of the cholesterol transporter genes Abcg5/g8 and Abca1, higher plasma cholesterol levels, and lower hepatic cholesterol levels compared with controls. These profound changes during fetal development did not affect cholesterol metabolism in adulthood nor did they influence coping with a high-fat/high-cholesterol diet. This study shows that the LXR system is functional in fetal mice and susceptible to pharmacological activation. Despite massive changes in fetal cholesterol metabolism, regulatory mechanisms involved in cholesterol metabolism return to a “normal” state in offspring and allow coping with a high-fat/high-cholesterol diet.

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Anti-hypercholesterolemic effect of Zingiber montanum extract

F1000Research ◽

10.12688/f1000research.16417.1 ◽

2018 ◽

Vol 7 ◽

pp. 1798

Author(s):

Swandari Paramita ◽

Meiliati Aminyoto ◽

Sjarif Ismail ◽

Enos Tangke Arung

Keyword(s):

Total Cholesterol ◽

High Fat Diet ◽

Diet Group ◽

High Density Lipoproteins ◽

Control Group ◽

High Cholesterol ◽

High Fat ◽

Cholesterol Levels ◽

White Rats ◽

Diet Control

Background: Hypercholesterolemia, high cholesterol levels in the blood, can contribute to many forms of disease, most notably cardiovascular disease. Anti-hypercholesterolemic agents generally used for those conditions have several side effects for patients. Zingiber montanum, known locally as “bangle”, belongs to the family Zingiberaceae and is a potential plants for alternative anti-hypercholesterolemic agents. This plant, from East Kalimantan, is used in traditional medicine for health problems caused by high cholesterol levels. The aim of this research was to find alternatives to anti-hypercholesterolemic agents, especially from natural sources. Methods: This study was an experimental study using 30 Wistar male white rats. Subjects were randomly divided into 6 groups (n=5): (1) normal control group; (2) high fat diet control group; (3) high fat diet with simvastatin; (4-6) high fat diet with Zingiber montanum extracts 100, 200, and 400 mg/kg. After 4 weeks of treatment, blood was collected from all groups, and plasma concentrations of triglycerides, total cholesterol, high density lipoproteins (HDL), and low density lipoproteins (LDL) were measured. Results: The results showed significant differences in total cholesterol (p=0.000), LDL (p=0.000) and triglycerides (p=0.001) in the high-fat diet group with Z. montanum extract, as compared to the high-fat diet control. Meanwhile, there were no significant differences in HDL levels (p=0.830) between the high-fat diet group and other groups. The results also showed significant differences in total cholesterol and LDLs for rats treated with Z. montanum extract, 100 mg/kg (p=0.000), 200 mg/kg (p=0.000), and 400 mg/kg (p=0.000) compared to the high-fat diet group. The result of Z. montanum 400 mg/kg also showed a significant reduction, not only for total cholesterol and LDLs, but also for triglycerides (p=0.030). Conclusion: It could be concluded that Z. montanum extracts have the potency to be further developed as a new natural source of the anti-hypercholesterolemic agents.

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Serum cholesterol levels and cancer mortality in 361,662 men screened for the Multiple Risk Factor Intervention Trial

JAMA ◽

10.1001/jama.257.7.943 ◽

1987 ◽

Vol 257 (7) ◽

pp. 943-948 ◽

Cited By ~ 32

Author(s):

R. W. Sherwin

Keyword(s):

Risk Factor ◽

Serum Cholesterol ◽

Cancer Mortality ◽

Multiple Risk Factor ◽

Intervention Trial ◽

Cholesterol Levels ◽

Multiple Risk

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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 ◽

10.3390/nu12020523 ◽

2020 ◽

Vol 12 (2) ◽

pp. 523 ◽

Cited By ~ 5

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.

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