This project studied the lowering blood lipids effect in atherosclerotic ApoE-deficient mice. Group A mice (n = 6), fed with a normal diet, served as the negative control. The experimental groups used mice fed with a high cholesterol diet (HCD) for eight weeks, and then selected for inclusion in the ...

Polyphenols extracted from grape seeds are able to inhibit amyloid-beta (Abeta) aggregation, reduce Abeta production and protect against Abeta neurotoxicity in vitro. We aimed to investigate the therapeutic effects of a polyphenol-rich grape seed extract (GSE) in Alzheimer's disease (AD) mice. APP(Swe)/PS1dE9 transgenic mice were fed with normal AIN-93G diet ...

Skeletal muscle is responsible for most of the insulin-stimulated glucose uptake and metabolism. Therefore, it plays an important role in the development of insulin resistance, one of the characteristics of the metabolic syndrome (MS). As the prevalence of the MS is increasing, there is an urgent need for more effective ...

Social and psychological factors interact with genetic predisposition and dietary habit in determining obesity. However, relatively few pre-clinical studies address the role of psychosocial factors in metabolic disorders. Previous studies from our laboratory demonstrated in male mice: 1) opposite status-dependent effect on body weight gain under chronic psychosocial stress; 2) ...

We investigated the potential usefulness of vesnarinone, a novel cytokine inhibitor, for the treatment of lung fibrosis using a murine model of bleomycin (BLM)-induced pulmonary fibrosis. Mice were fed a control diet (n=42), or a diet containing low (n=42) or high (n=42) dose of vesnarinone. Dietary intake of vesnarinone minimized ...

Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the ...

BACKGROUND: High-fat diets promote hepatic lipid accumulation. Paradoxically, these diets also induce lipogenic gene expression in rodent liver. Whether high expression of these genes actually results in an increased flux through the de novo lipogenic pathway in vivo has not been demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: To interrogate this apparent paradox, we ...

Cyclin kinase inhibitor p21 is one of the most potent inhibitors of aortic smooth muscle cell proliferation, a key mediator of atherosclerosis. This study tests if p2l deficiency will result in severe atherosclerosis in a mouse model. p21-/- and strain matched wild type mice were fed with high fat diet ...

BACKGROUND: The peripheral circadian clock in mice is entrained not only by light-dark cycles but also by daily restricted feeding schedules. Behavioral and cell culture experiments suggest an increase in glucose level as a factor in such feeding-induced entrainment. For application of feeding-induced entrainment in humans, nutrient content and dietary ...

BACKGROUND: Sepsis is a potentially deadly disease that often is caused by gram-positive bacteria, in particular Staphylococcus aureus (S. aureus). As there are few effective therapies for sepsis, increased basic knowledge about factors predisposing is needed. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study was to study the effect of Western ...

ABSTRACT: Hypercholesterolemia causes atherosclerosis in medium to large sized arteries. Cholesterol is less known for affecting the microvasculature and has not been previously reported to induce microvascular pathology in the central nervous system (CNS). Mice with a null mutation in the low-density lipoprotein receptor (LDLR) gene as well as C57BL/6J ...

BACKGROUND: PDZK1 is a four PDZ-domain containing protein that binds to the carboxy terminus of the HDL receptor, scavenger receptor class B type I (SR-BI), and regulates its expression, localization and function in a tissue-specific manner. PDZK1 knockout (KO) mice are characterized by a marked reduction of SR-BI protein expression ...

Hepatic fat deposition with hepatocellular damage, a feature of non-alcoholic fatty liver disease, is mediated by several putative factors including prostaglandins. In the present study, we examined whether group IVA phospholipase A(2) (IVA-PLA(2)), which catalyzes the first step in prostanoid biosynthesis, is involved in the development of fatty liver, using ...

BACKGROUND: Four genome-wide association studies mapped an "obesity" gene to human chromosome 10p11-12. As the zinc finger E-box binding homeobox 1 (ZEB1) transcription factor is encoded by the TCF8 gene located in that region, and as it influences the differentiation of various mesodermal lineages, we hypothesized that ZEB1 might also ...

The effect of diet supplemented with red beet (Beta vulgaris L.) leaf on antioxidant status of plasma and tissue was investigated in C57BL/6J mice. The mice were randomly divided into two groups after one-week acclimation, and fed a high fat (20%) and high cholesterol (1%) diet without (control group) or ...

Liver fatty acid binding protein (L-FABP) is highly expressed in both enterocytes and hepatocytes and binds multiple ligands, including saturated (SFA), unsaturated fatty acids (PUFA), and cholesterol. L-fabp (-/-) mice were protected against obesity and hepatic steatosis on a high saturated fat (SF), high cholesterol "Western" diet and manifested a ...

The obesity epidemic has generated interest in determining the contribution of various pathways to triglyceride synthesis, including an elucidation of the origin of triglyceride fatty acids and triglyceride glycerol. We hypothesized that a dietary intervention would demonstrate the importance of using glucose versus non-glucose carbon sources to synthesize triglycerides in ...

OBJECTIVE: The objective of our study was to determine whether methylenetetrahydrofolate reductase (Mthfr)-deficient mice develop preeclampsia (PE). STUDY DESIGN: Mice were placed on a normal or low-folate/high-methionine (LF/HM) diet to assess the impact of mild and severe homocysteinemia. Blood pressure and proteinuria were measured throughout gestation in Mthfr-deficient and control ...

Acid sphingomyelinase plays important roles in ceramide homeostasis, which has been proposed to be linked to insulin resistance. To test this association in vivo, acid sphingomyelinase deletion (asm(-/-)) was transferred to mice lacking the low density lipoprotein receptor (ldlr(-/-)), and then offsprings were placed on control or modified (enriched in ...

The current study examined the effects of Artemisia capillaris ethyl acetate (ACE) fraction on oxidative stress and antioxidant enzyme in high-fat diet induced obese mice. C57BL/6J mice were randomly assigned to normal diet group and high-fat diet groups. Normal diet groups were fed with an ACE fraction-free diet or 0.1 ...

The significance of transcription factors PPAR alpha, LXR alpha, and their responsive/target genes for the pathogenesis of atherosclerosis in apolipoprotein E and low-density lipoprotein receptor double deficient (AL) mice fed with high fat and cholesterol (HF) diet were studied. C57BL/6J wild-type (WT) mice were used as control to the AL ...

This study was performed to gain information about the influence of two cardiovascular risk factors, cigarette mainstream smoke (MS) and high-cholesterol/fat diet, on the progression of atherosclerosis in apolipoprotein E-deficient (Apo E-/-) mice. Eight to 12-week-old mice were whole-body exposed for up to 12 months (6h/day, 5 days/week) to diluted ...

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is predominantly expressed in liver and regulates cholesterol metabolism by down regulating liver LDL receptor (LDLR) proteins. Here we report transgenic overexpression of human PCSK9 in kidney increased plasma levels of PCSK9 and subsequently led to a dramatic reduction in liver LDLR proteins. The ...

Elemental diet (ED) has been used as an enteral nutritional therapy for Crohn's disease. However, the precise mechanisms of ED remain unclear. In interleukin-10 (IL-10)-deficient cell-transferred mice, we investigated the change of intestinal microbiota with ED using molecular terminal-restriction fragment length polymorphism (T-RFLP) analysis and culture method, and evaluated its ...

It was proposed that colon cancer induced by red and nitrite-preserved meat is due to meat-derived N-nitroso compounds in the colonic contents. To explore this view, we previously showed that feeding beef and hot dogs increased the fecal output of total apparent N-nitroso compounds (ANC) in mice. In the current ...

The molecular mechanisms responsible for alterations in lysine alpha-ketoglutarate reductase (LKR) activity are unknown. Therefore, the aim of these studies was to discern the mechanism(s) responsible for induction of hepatic LKR activity in rodents fed excess dietary protein. Four studies were conducted that used 84 mice. Mice were fed either ...

Sterol oxidation products derived from cholesterol and phytosterol are formed during the processing and storage of foods. The objective of the present study was to assess the potential unfavorable effects of oxysterols in mice. C57BL/6J mice were fed an AIN-93G-based diet containing 0.2 g/kg of oxycholesterol or oxyphytosterol for 4 ...

Chronic inflammation and increased visceral adipose tissue (VAT) are key elements of the metabolic syndrome. Both are considered to play a pathogenic role in the development of liver steatosis and insulin resistance. The aim of the present study was to investigate the hypothesis that an inflamed intestine, induced both by ...

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease in which the renin-angiotensin-aldosterone system plays an important role. Evidence indicate that the angiotensin type 1 receptor blockers can suppress atherogenesis, but the exact mechanisms have not been fully elucidated. The study was undertaken to investigate the potential effects and molecular mechanisms of ...

Obesity promotes insulin resistance and chronic inflammation. Disrupting any of several distinct steps in lipid synthesis decreases adiposity, but it is unclear if this approach coordinately corrects the environment that propagates metabolic disease. We tested the hypothesis that inactivation of FAS in the hypothalamus prevents diet-induced obesity and systemic inflammation. ...

The emergence of the whisker-related patterning of the barrel cortex during the first postnatal week is a frequently assessed feature of rodent cortical development and has been used extensively to screen for effects of genetic mutations on neural development in mice. As alterations in body weight often accompany genetic mutations, ...

Here we describe a study of the feasibility of lipid and phospholipid (PL) profiling using matrix assisted laser desorption/ionization (MALDI) Fourier transform mass spectrometry (FTMS) for two different applications. In this work PL profiles of different mammalian tissues as well as those of whole cell organisms were examined. In particular, ...

Growth differentiation factor 3 (GDF3) is a member of the TGFbeta superfamily. White adipose is one of the tissues in which Gdf3 is expressed, and it is the only tissue in which expression increases in response to high-fat diet. We generated Gdf3-/- mice, which were indistinguishable from wild-type mice and ...

Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D-tagatose (TAG; an isomer of fructose currently used as a low-calorie sweetener) on body weight, blood cholesterol concentrations, ...

Obesity is associated with diminished dopaminergic neurotransmission. It remains unclear whether this is a cause or a consequence of the obese state. We hypothesized that high fat feeding, a well known trigger of obesity in diet sensitive mice, would blunt dopaminergic neurotransmission prior to the development of insulin resistance. We ...

Hypertension and high serum cholesterol level are important risk factors for atherosclerosis and coronary heart disease. In the present study we tested the hypothesis whether high sodium intake, when given in combination with Western type high-fat diet, induces endothelial dysfunction and promotes atherosclerosis. Furthermore, the role and enzyme sources of ...

Oxidative stress drives many aging-associated problems. Because oxidative stress can be decreased by induction of phase 2 proteins, we hypothesized that incorporating the phase 2 protein inducer 2(3)-tert-butyl-4-hydroxyanisole (tBHA) into the diet would result in healthier aging. C57BL/6 mice were placed either on control mouse chow diet or on chow ...

Our previous study showed that mice fed a soft diet after weaning had reduced synaptic connections in the hippocampal formation and impaired spatial learning ability after 3 months of age. We hypothesized that soft-diet feeding during development reduced levels of brain-derived neurotrophic factor (BDNF) protein in the hippocampus, resulting in ...

Insulin resistance is an increasingly prevalent condition in humans that frequently clusters with disorders characterized by left ventricular (LV) pressure overload, such as systemic hypertension. To investigate the impact of insulin resistance on LV remodeling and functional response to pressure overload, C57BL6 male mice were fed a high-fat (HFD) or ...

It was proposed that colon cancer induced by red and nitrite-preserved meat is due to meat-derived N-nitroso compounds in the colonic contents. To explore this view, we previously showed that feeding beef and hot dogs increased the fecal output of total apparent N-nitroso compounds (ANC) in mice. In the current ...

The cyclin-dependent kinase inhibitor p57(kip2) regulates the cell cycle of trophoblastic cells. It has been established by a Japanese group that the heterozygous p57(kip2) knockout (p57(-/+)) mice are a good model of preeclampsia as they develop hypertension, proteinuria, and placental pathology. However, apart from the placental pathology, we could not ...

Food intake is controlled by peripheral signals from the gastrointestinal tract and adipocytes, which are integrated within the central nervous system. There is evidence that signals from the GI tract are modulated by long term changes in diet, possibly leading to hyperphagia and increased body weight. We tested the hypothesis ...

Several clinical trials have reported beneficial effects of the Ginkgo biloba extract EGb761 in the prevention and therapy of cognitive disorders including Alzheimer's disease (AD). The aim of the present long-term feeding trial was to study the impact of dietary EGb761 on Amyloid precursor protein (APP) metabolism in mice transgenic ...

Vascular contractility and endothelium-dependent vasodilatation were studied in mesenteric, aorta and coronary vasculature from male and female LDL receptor deficient (LDLR(-/-)) and wild type C57BL/6 mice fed either a high-fat Western Diet (WD) or regular animal chow (RD). Endothelium-dependent vasodilatation was also studied in small mesenteric arteries and aorta from ...

Metabolic syndrome has been reported to be associated with chronic kidney disease, but the mechanisms remain unclear. Although feeding of a high-fat diet (HFD) to C57BL/6 mice is reported to induce systemic metabolic abnormalities and subsequent renal injuries, such as albuminuria, similar to human metabolic syndrome, alterations in HFD-induced renal ...

Nonalcoholic steatohepatitis (NASH) comprises dysregulation of lipid metabolism and inflammation. Identification of the various genetic and environmental susceptibility factors for NASH may provide novel treatments to limit inflammation and fibrosis in patients. This study utilized a mouse model of hypercholesterolemia, low-density lipoprotein receptor knockout (LDLr(-/-)) mice fed a high-fat diet ...

We have generated a transgenic mouse model (MIP- LUC) that allows real-time imaging of insulin-secreting pancreatic beta cells in living mice. The beta cells of MIP- LUC transgenic mice emit a light signal that can be visualized externally by bioluminescent imaging using specialized equipment. In order to determine whether the ...

High-fat feeding in rodents leads to metabolic abnormalities mimicking the human metabolic syndrome, including obesity and insulin resistance. These metabolic diseases are associated with altered temporal organization of many physiological functions. The master circadian clock located in the suprachiasmatic nuclei controls most physiological functions and metabolic processes. Furthermore, under certain ...

To investigate the effect of a high-fat diet on brain and pancreas functions, we used SAMP10 mice that have characteristics of brain atrophy and cognitive dysfunction with aging. Simultaneously, we investigated the effect of green tea catechin consumption on high-fat diet feeding, because green tea catechin has been reported to ...

Lipids extracted from tsao-ko were separated into three fractions with silica gel column chromatography and fed to mice (3 mo old) for 90 d to clarify their inhibitory activity on digestive enzyme activity. The diets contained the following: control--no tsao-ko, 0.05% total lipid of tsao-ko (TL), 0.0109% chloroform fraction (CF), ...