• Asian-Australasian Journal of Animal Sciences
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• v.14 no.9
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• pp.1331-1341
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• 2001

Dairy cows are prone to fatty liver during the time of periparturient. Despite of the extensive studies, etiology and solutions for fatty liver are still not well known.The liver synthesizes triglycerides (TG) using precursors from bloodstream and secretes TG in form of very low density lipoprotein (VLDL) into bloodstream for the utilization by peripheral tissues. When the amount of TG synthesis exceeds the amount of secretion in VLDL-TG, TG accumulation within the liver occurs. Hepatic VLDL assembly and secretion involve multi-biochemical events.The availabilities of apolipoprotein B (apoB), E (apoE), microsomal triglyceride transfer protein (MTP) and soluble low density lipoprotein (LDL) receptor are now believed to be some of the main regulators for hepatic VLDL assembly and secretion. Studies in transgenic animals show that overexpression of these proteins stimulates VLDL production and secretion, which provides a possibility for alleviating bovine fatty liver by gene therapy. However, many problems remain to be solved to attain this goal. This review focuses on the molecular mechanisms of hepatic VLDL assembly and secretion, and the possibilities and problems of applying the knowledges to solve bovine fatty liver by gene therapy.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.

• Korean Journal of Clinical Pharmacy
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• v.27 no.3
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• pp.161-170
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• 2017

Background: There is recent evidence that insulin resistance is responsible for increasing the risk of developing cognitive dysfunction. To systematically review the influence of intranasal insulin treatment on the cognitive function in Alzheimer's disease patients. Methods: Randomized controlled trials comparing the cognitive effects of intranasal insulin therapy in Alzheimer's disease patients with controlled interventions were retrieved from Pubmed, Medline, Embase and Cochrane library. Meta-analysis was conducted on the cognitive measurements with a subgroup analysis by dose, gender and apolipoprotein E allele 4 (ApoE ${\varepsilon}4$) status. Results: Seven randomized controlled trials were eligible for inclusion. Intranasal insulin had a positive influence on the cognitive function as compared to placebo without a statistical significance (standardized mean difference; SMD = 0.109; 95% confidence interval; CI -0.04 to 0.26; P=0.14). In subgroup analysis, a 20 IU dose of intranasal insulin induced a significant improvement in cognitive function (SMD = 0.14; 95% CI 0.05 to 0.24; P=0.004), but 40 IU did not show this effect (SMD = -0.01; 95% CI -0.11 to 0.09; P=0.82). ApoE ${\varepsilon}4$ positive patients showed a significant decline in cognitive function as compared to ApoE ${\varepsilon}4$ positive patients in the control group (SMD = -0.213; 95% CI -0.38 to -0.04; P=0.015). Such an effect was not apparent in ApoE ${\varepsilon}4$ negative patients. Gender had no influence on the cognitive outcomes. Conclusion: The results indicate that intranasal insulin may have beneficial effect in improving the cognitive function in Alzheimer's disease patients.

• Dementia and Neurocognitive Disorders
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• v.21 no.1
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• pp.30-41
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• 2022

Background and Purpose: In this study we aimed to find the association between neuropsychological performance and body mass index (BMI) in patients with mild cognitive impairment (MCI). In addition, we investigated the effects of the apolipoprotein E (APOE) genotype in the relationship between the BMI and cognition in MCI. Methods: We enrolled a cohort of 3,038 subjects with MCI aged 65-90 from the Clinical Research Center for Dementia of South Korea and a dementia cohort of the Ewha Womans University Mokdong Hospital. MCI patients were classified into three subgroups according to the Asian standard of BMI. We compared cognitive performances between groups by one-way analysis of variance. To investigate the effects of the APOE genotype, we used multivariate linear regression models after adjusting for possible confounders. Results: Even though normal BMI groups were younger, had more females, and had less comorbidities, the higher BMI groups had better cognitive functions. Among subjects with APOE ε4 carriers, there was a positive relationship between the BMI and the memory task alone. Conclusions: Our findings suggested that higher BMI in patients with MCI were associated with better cognitive performance. The effects of the APOE ε4 genotype in the associations between BMI and cognition were distinguishing. Therefore, according to physical status, APOE ε4 genotype-specific strategies in the assessments and treatments may be necessary in elderly patients with MCI.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2001.12a
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• pp.61-68
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• 2001

Soybean, rice and nuts are the staple foods in South East Asia. In order to clarify the function of these foods in relation to coronary heart diseases, we have done a series of experiments using animals and humans. Soybean protein preparations (SPI) in comparison with an animal protein, casein (CAS), resulted in reducing atherosclerotic lesion development in apolipoprotein (apo) E deficient mice that develop an advanced lesion similar to that in humans. This action was attributed to the protein, since the ethanol-extracted SPI (EE-SPI), from which isoflavones and saponins removed, lowered the lesion development in apo E-deficient mice. However, The EE-SPI, compared to the SPI, resulted in a decrease of mRNA for key proteins of cholesterol metabolism (low density lipoprotein receptor and cholesterol 7$\alpha$-hydroxylase) in hypercholesterolemic rats, followed by an elevation of the serum cholesterol level, indicating a contribution of isoflavones to the serum cholesterol level. Rice protein (RPI) was also effective to lower the lesion development in apo E deficient mice. Both the SPI and RPI led to an increased level of the serum NOiN03, metabolites of NO. This effect appeared to be attributed to their high content of arginine. Besides, C57BL/6J mice fed a diet containing whole grain rice had an elevation of the serum high-density lipoprotein cholesterol. Furthermore, rice bran oil and the unsaponifiable fraction that is rich in plant sterols were effective to lower serum cholesterol levels in hypercholeserolemic rats. Finally, we tested if walnuts consumption would be hypocholesterolemic for Japanese. A diet containing walnuts effectively lowered the serum total and low density lipoprotein cholesterol in Japanese men and women. These animal and human experiments would be relevant to advocate publics to keep consuming diets including soybean, rice and nuts for their healthful life.

• Nutrition Research and Practice
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• v.17 no.6
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• pp.1099-1112
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• 2023

BACKGROUND/OBJECTIVES: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis. MATERIALS/METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk. RESULTS: The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice. CONCLUSIONS: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.1
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• pp.82-87
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• 2011

A study was conducted to determine the relationships between triacylglycerol (TAG) of plasma, very low density lipoprotein (VLDL) and fat deposition in two different breeds of chickens. The VLDL apolipoproteins of both breeds were also characterised. The breeds used were crossbred village chicken (AK) (Sasso crossed) and commercial broiler (CB) (Avian). They were housed in six pens with 30 female and 30 male birds of each breed per pen. Three male and three female birds from each pen were slaughtered and the blood was collected. The VLDL was isolated and sub-fractionated using Fast Protein Liquid Chromatography (FPLC). VLDL TAG of CB was significantly lower than AK. The particle size was negatively correlated with VLDL TAG and positively correlated with abdominal fat. Sub-fraction 2 contained more apo E that will enhance the lipolysis process of the VLDL TAG than subfraction 1. CB had a higher proportion of sub-fraction 2 than AK. The results showed that the proportion of sub-fraction 2 was negatively correlated with VLDL TAG concentration and positively correlated with abdominal fat.

• Journal of Oriental Neuropsychiatry
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• v.13 no.1
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• pp.53-77
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• 2002

Alzheimer's disease(AD) is a progressive neurodegenerative disease, which is pathologically characterized by neuritic plaques and neurofibrillary tangles associated with the acetylcholinesterase, apolipoprotein E and butylcholinesterase, and by mutations in the presenilin genes PS1 and PS2, and amyloid precursor proteins (APPs) overexpression. The present research is to examine the inhibitory effect of KGBH on PS1, PS2 and APPs overexpression detected by Western blotting. To verify the Effects of KGBH on cognitive deficits further, we tested it on the scopolamine(1mg/kg)-induced amnesia model of the mice using the Morris water maze tests, and there were ameliorative effects on memory impairment as a protection against scopolamine. KGBH only partially blocked the increase in blood serum level of acetylcholinesterase and Uric acid induced by scopolamine, where as blood glucose level was shown to attenuate the amnesia induced by scopolamine and inreased extracellular serum level. In conclusion, studies of KGBH that has been known as anti-choline and inhibitory ablilities of APPs overexpression, could also be used further as a important research data for a preventive and promising symptomatic treatment for Alzheimer's disease.

• Journal of Oriental Neuropsychiatry
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• v.14 no.1
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• pp.45-58
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• 2003

Alzheimer's disease(AD) is progressive neurodegenerative disease, which is pathologically characterized by neuritic plaques and neurofibrillary tangles associated with the acetylcholinesterase, apolipoprotein E and butylcholinesterase, and by mutations in the presenilin genes PS1 and PS2, and amyloid precursor proteins (APP) overexpression. The present research is to examine the inhibition effect of MDOF on PS-1, PS-2 and APP overexpression by detected to Western blotting. To verify the effects of MDOF on cognitive deficits further, we tested it on the scopolamine-induced amnesia model of the mice using the Morris water maze tests, and there was ameliorative effects of memory impairment as a protection to scopolamine. MDOF only partially blocked the increase in blood serum level of acetylcholinesterase and Uric acid induced by scopolamine, whereas blood glucose level was shown to attenuate the amnesia induced by scopolamine and inreased extracelluar serum level compared with only scopolamine injection. In conclusion, studies of MDOF that has been know as anti-choline and inhibition ablilities of APP overexpression, this could also be used further as a important research data for a preventive and promising symptomatic treatment for Alzheimer's disease.

• Journal of Oriental Neuropsychiatry
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• v.14 no.1
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• pp.59-74
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• 2003

Alzheimer's disease(AD) is a progressive neurodegenerative disease, which is pathologically characterized by neuritic plaques and neurofibrillary tangles associated with the acetylcholinesterase, apolipoprotein E and butylcholinesterase, and by mutations in the presenilin genes PS1 and PS2, and amyloid precursor proteins (APP) overexpression. The present research is to examine the inhibition effect of CPRT on PS-1, PS-2 and APP overexpression by detected to Western blotting. To verify the Effects of CPRT on cognitive deficits further, we tested it on the scopolamine-induced amnesia model of the mice using the Morris water maze tests, and there was ameliorative effects of memory impairment as a protection to scopolamine. CPRT only partially blocked the increase in blood serum level of acetylcholinesterase and Uric acid induced by scopolamine, whereas blood glucose level was shown to attenuate the amnesia induced by scopolamine and inreased extracellular serum level compared with only scopolamine injection. In conclusion, studies of CPRT that has been known as anti-choline and inhibition ablilities of APP overexpression, this could also be used further as a important research data for a preventive and promising symptomatic treatment for Alzheimer's disease.