Showing papers on "Normal diet published in 2009"

Functional Role of CD11c+ Monocytes in Atherogenesis Associated With Hypercholesterolemia

Abstract: Background— Monocyte activation and migration into the arterial wall are key events in atherogenesis associated with hypercholesterolemia. CD11c/CD18, a β2 integrin expressed on human monocytes and a subset of mouse monocytes, has been shown to play a distinct role in human monocyte adhesion on endothelial cells, but the regulation of CD11c in hypercholesterolemia and its role in atherogenesis are unknown. Methods and Results— Mice genetically deficient in CD11c were generated and crossbred with apolipoprotein E (apoE)−/− mice to generate CD11c−/−/apoE−/− mice. Using flow cytometry, we examined CD11c on blood leukocytes in apoE−/− hypercholesterolemic mice and found that compared with wild-type and apoE−/− mice on a normal diet, apoE−/− mice on a Western high-fat diet had increased CD11c+ monocytes. Circulating CD11c+ monocytes from apoE−/− mice fed a high-fat diet exhibited cytoplasmic lipid vacuoles and expressed higher levels of CD11b and CD29. Deficiency of CD11c decreased firm arrest of mouse monocyt...

Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice

Abstract: Caffeic acid (CA) and ellagic acid (EA) are phenolic acids naturally occurring in many plant foods. Cardiac protective effects of these compounds against dyslipidemia, hypercoagulability, oxidative stress and inflammation in diabetic mice were examined. Diabetic mice were divided into three groups (15 mice per group): diabetic mice with normal diet, 2% CA treatment, or 2% EA treatment. One group of non-diabetic mice with normal diet was used for comparison. After 12 weeks supplement, mice were sacrificed, and the variation of biomarkers for hypercoagulability, oxidative stress and inflammation in cardiac tissue of diabetic mice were measured. The intake of CA or EA significantly increased cardiac content of these compounds, alleviated body weight loss, elevated plasma insulin and decreased plasma glucose levels in diabetic mice (p < 0.05). These treatments also significantly enhanced plasma antithrombin-III and protein C activities (p < 0.05); and decreased triglyceride content in cardiac tissue and plasma (p < 0.05), in which the hypolipidemic effects of EA were significantly greater than that of CA (p < 0.05). CA or EA significantly lowered cardiac levels of malondialdehyde, reactive oxygen species, interleukin (IL)-beta, IL-6, tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1 (p < 0.05); and retained cardiac activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (p < 0.05). These compounds also significantly up-regulated cardiac mRNA expression of GPX1, SOD and catalase; and down-regulated IL-1beta, IL-6, TNF-alpha and MCP-1 mRNA expression in diabetic mice (p < 0.05). These results support that CA and EA could provide triglyceride-lowering, anti-coagulatory, anti-oxidative, and anti-inflammatory protection in cardiac tissue of diabetic mice. Thus, the supplement of these agents might be helpful for the prevention or attenuation of diabetic cardiomyopathy.

Extensive remyelination of the CNS leads to functional recovery

Abstract: Remyelination of the CNS in multiple sclerosis is thought to be important to restore conduction and protect axons against degeneration. Yet the role that remyelination plays in clinical recovery of function remains unproven. Here, we show that cats fed an irradiated diet during gestation developed a severe neurologic disease resulting from extensive myelin vacuolation and subsequent demyelination. Despite the severe myelin degeneration, axons remained essentially intact. There was a prompt endogenous response by cells of the oligodendrocyte lineage to the demyelination, with remyelination occurring simultaneously. Cats that were returned to a normal diet recovered slowly so that by 3-4 months they were neurologically normal. Histological examination of the CNS at this point showed extensive remyelination that was especially notable in the optic nerve where almost the entire nerve was remyelinated. Biochemical analysis of the diet and tissues from affected cats showed no dietary deficiencies or toxic accumulations. Thus, although the etiology of this remarkable disease remains unknown, it shows unequivocally that where axons are preserved remyelination is the default pathway in the CNS in nonimmune-mediated demyelinating disease. Most importantly, it confirms the clinical relevance of remyelination and its ability to restore function.

Minireview: the case for obesogens.

Abstract: Obesity and obesity-related disorders, such as type 2 diabetes, hypertension, and cardiovascular disease, are epidemic in Western countries, particularly the United States. The conventional wisdom holds that obesity is primarily the result of a positive energy balance, i.e. too many calories in and too few calories burned. Although it is self-evident that fat cannot be accumulated without a higher caloric intake than expenditure, recent research in a number of laboratories suggests the existence of chemicals that alter regulation of energy balance to favor weight gain and obesity. These obesogens derail the homeostatic mechanisms important for weight control, such that exposed individuals are predisposed to weight gain, despite normal diet and exercise. This review considers the evidence for obesogens, how they might act, and where future research is needed to clarify their relative contribution to the obesity epidemic.

mTOR complex 2 in adipose tissue negatively controls whole-body growth

Abstract: Mammalian target of rapamycin (mTOR), a highly conserved protein kinase that controls cell growth and metabolism in response to nutrients and growth factors, is found in 2 structurally and functionally distinct multiprotein complexes termed mTOR complex 1 (mTORC1) and mTORC2. mTORC2, which consists of rictor, mSIN1, mLST8, and mTOR, is activated by insulin/IGF1 and phosphorylates Ser-473 in the hydrophobic motif of Akt/PKB. Though the role of mTOR in single cells is relatively well characterized, the role of mTOR signaling in specific tissues and how this may contribute to overall body growth is poorly understood. To examine the role of mTORC2 in an individual tissue, we generated adipose-specific rictor knockout mice (rictor(ad-/-)). Rictor(ad-/-) mice are increased in body size due to an increase in size of nonadipose organs, including heart, kidney, spleen, and bone. Furthermore, rictor(ad-/-) mice have a disproportionately enlarged pancreas and are hyperinsulinemic, but glucose tolerant, and display elevated levels of insulin-like growth factor 1 (IGF1) and IGF1 binding protein 3 (IGFBP3). These effects are observed in mice on either a high-fat or a normal diet, but are generally more pronounced in mice on a high-fat diet. Our findings suggest that adipose tissue, in particular mTORC2 in adipose tissue, plays an unexpectedly central role in controlling whole-body growth.

Dietary nitrite prevents hypercholesterolemic microvascular inflammation and reverses endothelial dysfunction

Abstract: The nitrite anion is an endogenous product of mammalian nitric oxide (NO) metabolism, a key intermediate in the nitrogen cycle in plants, and a constituent of many foods. Research over the past 6 years has revealed surprising biological and cytoprotective activity of this anion. Hypercholesterolemia causes a proinflammatory phenotype in the microcirculation. This phenotype appears to result from a decline in NO bioavailability that results from a reduction in NO biosynthesis, inactivation of NO by superoxide, or both. Since nitrite has been shown to be potently cytoprotective and restore NO biochemical homeostasis, we investigated if supplemental nitrite could attenuate microvascular inflammation caused by a high cholesterol diet. C57Bl/6J mice were fed either a normal diet or a high cholesterol diet for 3 wk to induce microvascular inflammation. Mice on the high cholesterol diet received either nitrite-free drinking water or supplemental nitrite at 33 or 99 mg/l ad libitum in their drinking water. The results from this investigation reveal that mice fed a cholesterol-enriched diet exhibited significantly elevated leukocyte adhesion to and emigration through the venular endothelium as well as impaired endothelium-dependent relaxation in arterioles. Administration of nitrite in the drinking water inhibited the leukocyte adhesion and emigration and prevented the arteriolar dysfunction. This was associated with sparing of reduced tetrahydrobiopterin and decreased levels of C-reactive protein. These data reveal novel anti-inflammatory properties of nitrite and implicate the use of nitrite as a new natural therapy for microvascular inflammation and endothelial dysfunction associated with hypercholesterolemia.

Diet-induced obesity in female mice leads to peroxidized lipid accumulations and impairment of hippocampal neurogenesis during the early life of their offspring

Abstract: Maternal obesity may affect the child's long-term development and health. However, there is little information about the involvement of maternal obesity in the brain development of offspring. Here, we investigated the effects of maternal obesity on the hippocampal formation of offspring. Adult female mice were fed either a normal diet (ND, 4% fat) or a high-fat diet (HFD, 32% fat) 6 wk before mating and throughout pregnancy and the majority of lactation. We found that infants from HFD-fed dams (HFD offspring) showed obesity and hyperlipidemia during suckling. In HFD offspring, lipid peroxidation was promoted in serum and the hippocampal dentate gyrus, where neurogenesis takes place throughout postnatal life. Using a BrdU-pulse labeling study, we showed that malondialdehyde, a product of peroxidized lipids, reduced the proliferation of hippocampal progenitor cells in vitro and that neurogenesis in HFD offspring during postnatal development was similarly lowered relative to the ND animals. These results indicated that maternal obesity impairs hippocampal progenitor cell division and neuronal production in young offspring possibly due to metabolic and oxidative changes.

Statin Therapy Inhibits Remyelination in the Central Nervous System

Abstract: Remyelination of lesions in the central nervous system contributes to neural repair following clinical relapses in multiple sclerosis. Remyelination is initiated by recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Simvastatin, a blood-brain barrier-permeable statin in multiple sclerosis clinical trials, has been shown to impact the in vitro processes that have been implicated in remyelination. Animals were fed a cuprizone-supplemented diet for 6 weeks to induce localized demyelination in the corpus callosum; subsequent return to normal diet for 3 weeks stimulated remyelination. Simvastatin was injected intraperitoneally during the period of coincident demyelination and OPC maturation (weeks 4 to 6), throughout the entire period of OPC responses (weeks 4 to 9), or during the remyelination-only phase (weeks 7 to 9). Simvastatin treatment (weeks 4 to 6) caused a decrease in myelin load and both Olig2strong and Nkx2.2strong OPC numbers. Simvastatin treatment (weeks 4 to 9 and 7 to 9) caused a decrease in myelin load, which was correlated with a reduction in Nkx2.2strong OPCs and an increase in Olig2strong cells, suggesting that OPCs were maintained in an immature state (Olig2strong/Nkx2.2weak). NogoA+ oligodendrocyte numbers were decreased during all simvastatin treatment regimens. Our findings suggest that simvastatin inhibits central nervous system remyelination by blocking progenitor differentiation, indicating the need to monitor effects of systemic immunotherapies that can access the central nervous system on brain tissue-repair processes.

Comparison of three common tonsillectomy techniques: a prospective randomized, double-blinded clinical study.

Abstract: Objective: To evaluate three current tonsillectomy techniques—intracapsular microdebridement, intracapsular coblation, and traditional extracapsular electrocautery dissection—comparing surgical parameters, efficacy, and morbidity in the treatment for obstructive sleep disordered breathing in children. Study Design: Prospective, double-blinded study with follow-up by telephone interview. Method: From February 2004 to July 2006, a total of 156 patients between the ages of 6 months and 22 years scheduled for adenotonsillectomy were randomly assigned to electrocautery, coblator, and microdebrider groups. Outcome Measures: 1) Patient demographics; 2) Intraoperative time; 3) Surgeon's perception of difficulty; 4) Indicators of postoperative morbidity: pain, use of pain medication, return to diet, and activity level; 5) Complications; 6) Cost. Results: Microdebrider technique produced the shortest total surgical time, averaging 16 minutes. Use of coblation resulted in 2 less days of pain medication compared to electrocautery. Patients in the coblator and microdebrider groups returned to a normal diet 1.51 days and 1.77 days earlier, respectively, than in the electrocautery group. They also returned to preoperative activity levels 1.85 days and 2.06 days earlier than in the electrocautery group. Of all three methods, the microdebrider was the most cost effective. The coblator and microdebrider did not differ significantly from each other in all other parameters. The three techniques showed no statistically significant difference in assessment of difficulty, average pain scores, or postoperative complications. Conclusions: Postoperative recovery following intracapsular adenotonsillectomy in children with obstructive sleep apnea is significantly earlier with use of either the coblator or microdebrider versus traditional extracapsular tonsillectomy with electrocautery. Microdebrider and coblator were comparable in all other areas except for shorter operative time and less cost for the microdebrider. Laryngoscope, 119:162–170, 2009

High dietary inorganic phosphate increases lung tumorigenesis and alters Akt signaling.

Abstract: Rationale: Phosphate (Pi) is an essential nutrient to living organisms. Recent surveys indicate that the intake of Pi has increased steadily. Our previous studies have indicated that elevated Pi activates the Akt signaling pathway. An increased knowledge of the response of lung cancer tissue to high dietary Pi may provide an important link between diet and lung tumorigenesis. Objectives: The current study was performed to elucidate the potential effects of high dietary Pi on lung cancer development. Methods: Experiments were performed on 5-week-old male K-rasLA1 lung cancer model mice and 6-week-old male urethane-induced lung cancer model mice. Mice were fed a diet containing 0.5% Pi (normal Pi) and 1.0% Pi (high Pi) for 4 weeks. At the end of the experiment, all mice were killed. Lung cancer development was evaluated by diverse methods. Measurement and Main Results: A diet high in Pi increased lung tumor progression and growth compared with normal diet. High dietary Pi increased the sodium-dependent inorganic phosphate transporter-2b protein levels in the lungs. High dietary consumption of Pi stimulated pulmonary Akt activity while suppressing the protein levels of tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 as well as Akt binding partner carboxyl-terminal modulator protein, resulting in facilitated cap-dependent protein translation. In addition, high dietary Pi significantly stimulated cell proliferation in the lungs of K-rasLA1 mice. Conclusions: Our results showed that high dietary Pi promoted tumorigenesis and altered Akt signaling, thus suggesting that careful regulation of dietary Pi may be critical for lung cancer prevention as well as treatment.

Dietary exclusions for improving established atopic eczema in adults and children: systematic review.

Abstract: Atopic eczema is the most common inflammatory skin disease of childhood in developed countries. We performed a systematic review of randomized controlled trials to assess the effects of dietary exclusions for the treatment of established atopic eczema. Nine trials (421 participants) were included, most of which were poorly reported. Six were studies of egg and milk exclusion (n = 288), one was a study of few foods (n = 85) and two were studies of an elemental diet (n = 48). There appears to be no benefit of an egg- and milk-free diet in unselected participants with atopic eczema. There is also no evidence of benefit in the use of an elemental or few-foods diet in unselected cases of atopic eczema. There may be some benefit in using an egg-free diet in infants with suspected egg allergy who have positive specific IgE to eggs - one study found 51% of the children had a significant improvement in body surface area with the exclusion diet as compared with normal diet (95% CI 1.07-2.11) and change in surface area and severity score was significantly improved in the exclusion diet as compared with the normal diet at the end of 6 weeks (MD 5.50, 95% CI 0.19-10.81) and end of treatment (MD 6.10, 95% CI 0.06-12.14). Despite their frequent use, we find little good quality evidence to support the use of exclusion diets in atopic eczema.

Developmental stress affects song learning but not song complexity and vocal amplitude in zebra finches

Abstract: Several recent studies have tested the hypothesis that song quality in adult birds may reflect early developmental conditions, specifically nutritional stress during the nestling period. Whilst all of these earlier studies found apparent links between early nutritional stress and song quality, their results disagree as to which aspects of song learning or production were affected. In this study, we attempted to reconcile these apparently inconsistent results. Our study also provides the first assessment of song amplitude in relation to early developmental stress and as a potential cue to male quality. We used an experimental manipulation in which the seeds on which the birds were reared were mixed with husks, making them more difficult for the parents to obtain. Compared with controls, such chicks were lighter at fledging; they were thereafter placed on a normal diet and had caught up by 100 days. We show that nutritional stress during the first 30 days of life reduced the birds’ accuracy of song syntax learning, resulting in poorer copies of tutor songs. Our experimental manipulations did not lead to significant changes in song amplitude, song duration or repertoire size. Thus, individual differences observed in song performance features probably reflect differences in current condition or motivation rather than past condition.

Impaired function of coronary BKCa channels in metabolic syndrome

Abstract: The role of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels in regulation of coronary microvascular function is widely appreciated, but molecular and functional changes underlying the deleterious influence of metabolic syndrome (MetS) have not been determined. Male Ossabaw miniature swine consumed for 3-6 mo a normal diet (11% kcal from fat) or an excess-calorie atherogenic diet that induces MetS (45% kcal from fat, 2% cholesterol, 20% kcal from fructose). MetS significantly impaired coronary vasodilation to the BK(Ca) opener NS-1619 in vivo (30-100 microg) and reduced the contribution of these channels to adenosine-induced microvascular vasodilation in vitro (1-100 microM). MetS reduced whole cell penitrem A (1 microM)-sensitive K(+) current and NS-1619-activated (10 microM) current in isolated coronary vascular smooth muscle cells. MetS increased the concentration of free intracellular Ca(2+) and augmented coronary vasoconstriction to the L-type Ca(2+) channel agonist BAY K 8644 (10 pM-10 nM). BK(Ca) channel alpha and beta(1) protein expression was increased in coronary arteries from MetS swine. Coronary vascular dysfunction in MetS is related to impaired BK(Ca) channel function and is accompanied by significant increases in L-type Ca(2+) channel-mediated coronary vasoconstriction.

Cholesterol diet-induced hyperlipidemia impairs the cardioprotective effect of postconditioning: role of peroxynitrite

Abstract: The aim of the present study was to investigate if hyperlipidemia interferes with the infarct size-limiting effect of postconditioning and to study the involvement of peroxynitrite in this phenomenon. Rats were fed a 2% cholesterol-enriched or normal diet for 12 wk. Infarct size by triphenyltetrazolium chloride staining was measured in hearts isolated from both groups and subjected to 30 min coronary occlusion followed by 120 min reperfusion with or without the postconditioning protocol induced by six cycles of 10 s coronary occlusion and 10 s reperfusion at the onset of the reperfusion. Postconditioning significantly decreased infarct size in the normolipidemic but not in the hyperlipidemic group. Postconditioning increased cardiac 3-nitrotyrosine concentration (a marker for peroxynitrite formation) in the normal but not in the cholesterol-fed group when measured at the 5th min of reperfusion. Next, we tested if the postconditioning-induced acute increase in peroxynitrite is involved in the cardioprotection in normolipidemic animals in separate experiments. Postconditioning failed to decrease infarct size in the presence of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-iron [III] (20 mg/l) in normolipidemic animals. We conclude that an early increase in peroxynitrite after postconditioning plays a role in cardioprotection. Furthermore, hyperlipidemia blocks the cardioprotective effect of postconditioning at least in part via deterioration of the postconditioning-induced early increase in peroxynitrite formation.

Erythropoietin Over-Expression Protects against Diet-Induced Obesity in Mice through Increased Fat Oxidation in Muscles

Abstract: 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 metabolic effect of EPO in vivo. At 12 weeks, EPO expression resulted in a 23% weight reduction (P<0.01) in EPO transfected obese mice; thus the mice weighed 21.9±0.8 g (control, normal diet,) 21.9±1.4 g (EPO, normal diet), 35.3±3.3 g (control, high-fat diet) and 28.8±2.6 g (EPO, high-fat diet). Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass. The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance in the high-fat fed mice. EPO expression also induced a 14% increase in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles. In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles.

Autoantibodies against epidermal transglutaminase are a sensitive diagnostic marker in patients with dermatitis herpetiformis on a normal or gluten-free diet

Abstract: Background Dermatitis herpetiformis (DH) is a cutaneous manifestation of gluten-sensitive enteropathy (celiac disease). Patients with DH demonstrate circulating IgA antibodies against epidermal transglutaminase (eTG) and tissue transglutaminase (tTG). It has been suggested that eTG is the autoantigen of DH. Objective The purpose of this study was to characterize the autoimmune response to eTG and tTG in patients with DH on a normal or gluten-free diet (GFD). Methods Sera from 52 patients with DH were studied for the presence of IgA antibodies to eTG and tTG by enzyme-linked immunosorbant assay. In 38 patients, serum was obtained before initiation of a GFD, whereas 14 patients had been on a GFD for at least 2 years. Results Autoantibodies against eTG were detected in 36 of 38 patients (95%) and those against tTG in 30 of 38 patients (79%) with DH on a normal diet. Of 14 patients on a long-term GFD, 7 patients were free of DH lesions and did not require dapsone treatment. None of these patients showed circulating antibodies against eTG or tTG. The remaining 7 patients on a GFD were not able to stop taking dapsone. All these patients demonstrated anti-eTG antibodies, whereas only 3 of them showed additional reactivity against tTG. Limitation Autoantibody levels against eTG and tTG before and after introduction of a GFD were not examined in the same patients. Conclusion Our data suggest that antibodies to eTG are the most sensitive serologic marker in treated and untreated patients with DH and confirm the central role of eTG in the pathogenesis of this disease. (J Am Acad Dermatol 2009;61:39-43.)

Outcomes of Salvage Surgery With Free Flap Reconstruction for Recurrent Oral and Oropharyngeal Cancer

Abstract: Objectives/Hypothesis: To evaluate outcomes of salvage surgery with free flap reconstruction for recurrent squamous cell carcinoma of the oropharynx and oral cavity with increased use of chemoradiotherapy. Study Design: Retrospective patient review. Methods: All patients undergoing salvage surgery with free flap reconstruction for oropharynx (n = 36) and oral cavity (n = 36) squamous cell carcinomas between January 2001 and January 2008 were obtained. Mean follow-up was 14 months. Previous chemoradiotherapy was used in 40% and radiotherapy alone in 60%. Results: Complications were more frequent in oropharynx than oral cavity tumors (36% and 14%, respectively; P = .05) requiring more secondary procedures (15 for oropharynx vs. six for oral cavity). Few patients returned to a normal diet (8%), and a majority retained an enterogastric feeding tube (56%). Median survival overall following salvage surgery was 44.8 months for oral cavity and 53.8 months for oropharynx head and neck squamous cell carcinoma. Overall estimated 1-, 2-, and 5-year observed survivals were 98%, 77.2%, and 43.7%, respectively. Twelve patients had a disease-free interval of <6 months, 92% of whom died of disease. Of 17 patients with disease at the primary site and involved regional lymph nodes, 94% died of disease. Conclusions: Salvage surgery with free flap reconstruction for recurrent oral and oropharyngeal tumors after chemoradiotherapy has acceptable morbidity and similar cure rates as salvage following radiotherapy without chemotherapy. Concurrent nodal recurrence and short disease-free interval are associated with reduced cure rates. A significant proportion will require enterogastric feeding and few will tolerate a normal diet.

Obesity is the major contributor to vascular dysfunction and inflammation in high fat diet hypertensive rats

Abstract: Obesity and hypertension are the two major risk factors that contribute to the progression of end-stage renal disease. To examine whether hypertension further exacerbates oxidative stress and vascular dysfunction and inflammation in obese rats, four groups of male Sprague-Dawley rats were fed either a normal (7% fat) or high-fat (36% fat) diet for 6 weeks and osmotic pumps were implanted to deliver ANG (angiotensin II) or vehicle for an additional 4 weeks.Treatment with the high-fat diet did not alter ANG-induced hypertension compared with the normal diet (174 +/- 6 compared with 170 +/- 5 mmHg respectively). Treatment with the high-fat diet increased body weight gain and plasma leptin levels and induced insulin resistance in normotensive and ANG-induced hypertensive rats. Plasma TBARS (thiobarbituric acid-reacting substances), a measure of oxidative stress, were elevated in high-fat diet-fed rats compared with controls (11.2 +/-1 compared with 8.4 +/- nmol/ml respectively) and was increased further in ANG-induced hypertensive rats fed a high-fat diet (18.8 +/-2.2 nmol/ml). Urinary nitrite excretion was also decreased in rats fed a high-fat diet without or with ANG infusion compared with controls. Afferent arteriolar relaxation to acetylcholine was impaired in rats fed the high-fat diet without or with ANG infusion. Renal cortical TNF-alpha(tumour necrosis factor-alpha), COX-2(cyclo-oxygenase-2) and phospho-IKK (inhibitor of nuclear factor k B kinase) expression increased in high-fat diet-fed rats compared with normal diet-fed rats. The increases in phospho-IKK and COX-2 expression were elevated further in ANG-induced hypertensive rats fed the high-fat diet.These results suggest that ANG-induced hypertension exacerbates oxidative stress and renal inflammation without further impairment in vascular dysfunction in high-fat diet-induced obesity.

Evidence-Based Review on the Effect of Normal Dietary Consumption of Fructose on Development of Hyperlipidemia and Obesity in Healthy, Normal Weight Individuals

Abstract: In recent years, there has been episodic speculation that an increase in consumption of fructose from foods and beverages is an underlying factor responsible for the relatively recent increase in obesity and obesity-related diseases such as diabetes. Reports in support of this hypothesis have been published, showing that concentrations of triglycerides (TG) are higher and concentrations of insulin and hormones associated with satiety are lower in animals following the ingestion of fairly large quantities of fructose, compared to other carbohydrates. However, results from human studies are inconsistent. A possible reason for the inconsistent results is that they are dependent on the particular study population, the design of the studies, and/or the amount of fructose administered. A systematic assessment of the strength and quality of the studies and their relevance for healthy, normal weight humans ingesting fructose in a normal dietary manner has not been performed. The purpose of this review was to critically evaluate the existing database for a causal relationship between the ingestion of fructose in a normal, dietary manner and the development of hyperlipidemia or increased body weight in healthy, normal weight humans, using an evidence-based approach. The results of the analysis indicate that fructose does not cause biologically relevant changes in TG or body weight when consumed at levels approaching 95th percentile estimates of intake.

Atherosclerosis-Preventing Activity of Lactic Acid Bacteria-Fermented Milk−Soymilk Supplemented with Momordica charantia

Abstract: In this study, the milk−soymilk and milk−soymilk supplemented with Momordica charantia, a common oriental vegetable possessing medicinal activities, were fermented by lactic bacteria. The objective of this study was to investigate the effects of milk−soymilk and fermented milk−soymilk with or without M. charantia on atherosclerosis in hyperlipidemic hamsters. Fermented 25% milk and 75% soymilk combinations, supplemented with 1% M. charantia solution, can improve the acceptability of the fermented beverage. A total of 72 male Golden Syrian hamsters were divided into 9 groups (n = 8/group), and experimental diets were provided with a normal diet for the normal group and a high-cholesterol diet for others. The milk−soymilk and fermented milk−soymilk with or without M. charantia were administrated for 8 weeks. The milk−soymilk and fermented milk−soymilk with and without M. charantia were able to significantly decrease (p < 0.05) the serum cholesterol and the atherosclerotic plaque in aorta based on the compar...

1H-nuclear magnetic resonance spectroscopy-based metabolic assessment in a rat model of obesity induced by a high-fat diet

Abstract: Obesity, whose prevalence is increasing rapidly worldwide, is recognized as a risk factor for diabetes, cardiovascular disease, liver disease, and renal disease To investigate metabolic changes in the urine of a rat model of obesity induced by a high-fat diet (HFD), rats were divided into the following four groups based on the diet type and degree of weight gain: normal-diet (ND) low gainers, ND high gainers, HFD low gainers, and HFD high gainers Biochemical analyses of visceral fat-pad weight, plasma, and liver tissues were performed The (1)H-nuclear magnetic resonance ((1)H-NMR) spectra of urine were analyzed using multivariate statistical analysis to identify the separation of the groups It was observed that the metabolic profile of urine obtained by (1)H-NMR-spectroscopy-based metabolomic analysis differed between ND low gainers and ND high gainers even though these animals consumed the same normal diet Several key metabolites in urine, such as betaine, taurine, acetone/acetoacetate, phenylacetylglycine, pyruvate, lactate, and citrate contributed to the classification of these two groups The metabolic profile of urine also differed between ND low gainers and HFD high gainers, which consumed the different diet and showed a different weight gain This study has identified features of urine metabolites in various groups and demonstrated the reliability of an NMR-based metabolomics approach to investigate the effects of the diet and the physical constitution on obesity

Development of Obesity is Associated with Increased Calories per Meal Rather than per Day. A Study of High-Fat Diet-Induced Obesity in Young Rats

Abstract: We challenge the current belief that obesity is a result of overnutrition by studying a rodent model of human obesity. Male Sprague-Dawley rats at 3 weeks of age were fed with a mixed normal diet of 10% fat and high-fat diet of 60% fat (50:50) for 2 weeks and then turned to 100% high-fat diet until 43 weeks of age. Body weight gain was recorded, and food intake, eating behavior, and metabolic variables were measured by a comprehensive laboratory animal monitoring system. Body composition was determined by dual-energy X-ray absorptiometry. Ghrelin/obestatin-producing A-like cells in the stomach were analyzed by immunohistochemistry. Rats on high-fat diet were overweight at 9 weeks of age and later became obese characterized by increased body weight and excess fat deposition. There were no obesity-prone, obesity middle tertile, and obesity-resistant subgroups in rats on high-fat diet. The young rats on high-fat diet, even before becoming overweight (i.e., 8 weeks), consumed larger portion of meal (kilocalorie per meal) and ate faster but less frequent than the rats on normal diet. Obese rats had reduced food intake (expressed as gram per 100-g body weight per 24 h), unchanged calorie intake (kilocalorie per 100-g body weight per 24 h), and energy expenditure (kilocalorie per hour per 100-g body weight), and increased number of A-like cells in the stomach. Large size of meal, but not overnutrition, appears to be responsible for high-fat diet-induced obesity in rats. We propose a consideration that prevention strategies for obesity epidemic should strongly focus on meal size at early childhood and adolescence.

Comparison of the antiobesity effects of the protopanaxadiol- and protopanaxatriol-type saponins of red ginseng.

Abstract: A previous study demonstrated that ginseng crude saponins prevent obesity induced by a high-fat diet in rats. Ginseng crude saponins are known to contain a variety of bioactive saponins. The present study investigated and compared the antiobesity activity of protopanaxadiol (PD) and protopanaxatriol (PT) type saponins, major active compounds isolated from crude saponins. Male 4-week-old Sprague-Dawley rats were fed with normal diet (N) or high-fat diet (HF). After 5 weeks, the HF diet group was subdivided into the control HF diet, HF diet-PD and HF diet-PT group (50 mg/kg/day, 3 weeks, i.p.). Treatment with PD and PT in the HF diet group reduced the body weight, total food intake, fat contents, serum total cholesterol and leptin to levels equal to or below the N diet group. The hypothalamic expression of orexigenic neuropeptide Y was significantly decreased with PD or PT treatment, whereas that of anorexigenic cholecystokinin was increased, compared with the control HF diet group. In addition, PD type saponins had more potent antiobesity properties than PT saponins, indicating that PD-type saponins are the major components contributing to the antiobesity activities of ginseng crude saponins. The results suggest that the antiobesity activity of PD and PT type saponins may result from inhibiting energy gain, normalizing hypothalamic neuropeptides and serum biochemicals related to the control of obesity.

The Physiologic Effects of Caloric Restriction Are Reflected in the in Vivo Adipocyte-Enriched Proteome of Overweight/Obese Subjects

Abstract: We have applied our recently designed proteomics apparoach to search for protein changes in the in vivo adipocyte-enriched proteome from 8 overweight/obese subjects who underwent an intervention of 5 weeks of a very low calorie diet followed by 3 weeks of a normal diet. On average, persons lost 9.5 kg body weight largely contributed by the loss of fat mass (7.1 kg). Various parameters of adiposity and lipid metabolism changed significantly. Proteomics analysis revealed 6 significantly changed proteins. Analysis indicates that fructose-bisphosphate aldolase C and tubulin beta 5 are potential biomarkers for the present intervention. Further, identified proteins indicate a reduced intracellular scaffolding of GLUT4 (ALDOC, TUBB5, ANXA2), an increased uptake of fatty acids (FABP4), an improved inflammatory profile of the adipose tissue (ApoA1, AOP1) and a change in fat droplet organization (vimentin). Correlation analysis between changes in protein spot intensities and parameters of adiposity or lipid metabolism points to a link between aldo-ketoreductase 1C2 and parameters of adiposity, between FABP4 and parameters of lipid metabolism, and between proteins for beta-oxidation (HADH, ACADS, ACAT1) and FFA levels. Altogether, our findings underscore the potential value of in vivo proteomics for human intervention studies.