An Urban Diet Impairs Tibial Vasodilation in Mourning Doves (Zenaida macroura)

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Description
Birds maintain resting plasma glucose concentrations (pGlu) nearly twice that of comparably sized mammals. Despite this, birds do not incur much of the oxidative tissue damage that might be expected from a high pGlu. Their ability to stave off oxidative

Birds maintain resting plasma glucose concentrations (pGlu) nearly twice that of comparably sized mammals. Despite this, birds do not incur much of the oxidative tissue damage that might be expected from a high pGlu. Their ability to stave off oxidative damage allows birds to serve as a negative model of hyperglycemia-related complications, making them ideal for the development of new diabetes treatments with the potential for human application. Previous studies conducted by the Sweazea Lab at Arizona State University aimed to use diet as a means to raise blood glucose in mourning doves (Zenaida macroura) in order to better understand the mechanisms they utilize to stave off oxidative damage. These protocols used dietary interventions—a 60% high fat (HF) “chow” diet, and a high carbohydrate (HC) white bread diet—but were unsuccessful in inducing pathologies. Based on this research, we hypothesized that a model of an urban diet (high in fat, refined carbohydrates, and sodium) might impair vasodilation, as the effect of this diet on birds is currently unknown. We found that tibial vasodilation was significantly impaired in birds fed an urban diet compared to those fed a seed diet. Unexpectedly, vasodilation in the urban diet group was comparable to data of wild-caught birds from previous research, possibly indicating that the birds had already been eating a diet similar to this study’s urban diet before they were caught. This may constitute evidence that the seed diet improved vasodilation while the urban diet more closely mimicked the diet of the birds before the trial, suggesting that the model of the urban diet acted as the control diet in this context. This study is the first step in elucidating avian mechanisms for dealing with diabetogenic diets and has potential to aid in the development of treatments for humans with metabolic syndrome.
Date Created
2020-05
Agent

The Effects of Antiseptic Mouthwash Use and Sodium Intake on Systemic Blood Pressure Regulation and Salivary Nitrate Levels: A Randomized Controlled Crossover Trial

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Description
Background. Despite extensive research in the literature aimed at understanding the role of hypertension as a major risk factor for numerous leading causes of death in the United

States, rates of this disease continue to rise. Recent findings suggest that antiseptic

Background. Despite extensive research in the literature aimed at understanding the role of hypertension as a major risk factor for numerous leading causes of death in the United

States, rates of this disease continue to rise. Recent findings suggest that antiseptic mouthwash use may increase blood pressure through elimination of oral bacteria that facilitate the enterosalivary nitrate-nitrite-nitric oxide pathway.

Objective. The purpose of this randomized, controlled, crossover trial was to examine the effects of antiseptic mouthwash use and sodium intake on blood pressure and salivary nitrate levels in prehypertensive adults.

Methods. Healthy adults (n=10; 47.3±12.5) with mildly elevated blood pressure (average baseline blood pressure of 114.9/75.2 mmHg) were recruited and were randomly assigned to a control condition, antiseptic mouthwash use, or antiseptic mouthwash use + consumption of three pickles per day (~6000 mg/day of sodium) for a total of 7 days. Given the crossover design of this study, participants adhered to a 1-week washout period between each condition and all participants received all three treatments. Findings were considered significant at a p-value of <0.05 and a repeated measures ANOVA test was used to compare change data of each condition.

Results. Changes in systolic and diastolic blood pressure were not statistically significant (p=0.469 and p=0.859, respectively). Changes in salivary nitrite levels were not statistically significant (p=0.493). Although there appeared to be fluctuations in sodium intake between interventions, differences in sodium intake were not statistically significant when pickles were not accounted for (p=0.057).

Conclusion. Antiseptic mouthwash use did not appear to induce significant changes in systolic or diastolic blood pressure in this population.
Date Created
2019
Agent

Systematic Review of the Impact of Genistein on Diabetes Related Outcomes

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Description
As the 7th leading cause of death in the world, with over 1.6 millions deaths attributed to it in 2016 alone, diabetes mellitus has been a rising global health concern. Type 1 diabetes is caused by lack of insulin production

As the 7th leading cause of death in the world, with over 1.6 millions deaths attributed to it in 2016 alone, diabetes mellitus has been a rising global health concern. Type 1 diabetes is caused by lack of insulin production whereas type 2 diabetes is caused by insulin resistance. Both types of diabetes lead to increased glucose levels in the body if left untreated. This, in turn, leads to the development of a host of complications, one of which is ischemic heart disease. Accounting for the death of 16% of the world’s population, ischemic heart disease has been the leading cause of death since 2000. As of 2019, deaths from this disease have risen from 2 million to over 8.9 million globally. While medicine exists to counter the negative outcomes of diabetes mellitus, lower income nations suffer from the lack of availability and high costs of these medications. Therefore, this systematic review was performed to determine whether a non-medicinal treatment could provide similar therapeutic benefits for individuals with diabetes. Genistein is a phytoestrogen found in soy-based products, which has been potentially linked with preventing diabetes and improving diabetes-related symptoms such as hyperglycemia and abnormal insulin levels. We searched PubMed and SCOPUS using the terms ‘genistein’, ‘diabetes’, and ‘glucose’ and identified 32 peer-reviewed articles. In general, preclinical studies demonstrate that genistein decreases body weight as well as circulating glucose and triglycerides concentrations while increasing insulin levels and insulin sensitivity. It also delayed the onset of type 1 and type 2 diabetes. In contrast, clinical studies of genistein in general reported no significant relationship between genistein and body mass, circulating glucose, serum insulin, A1C concentrations, or onset of type 1 diabetes. However, genistein was found to improve insulin sensitivity, delay type 2 diabetes onset and improve serum triglyceride levels. In summary, preclinical and clinical studies suggest that genistein may help delay onset of type 2 diabetes and improve several symptoms associated with the disease. By translating these findings into clinical settings, genistein may offer a cost effective natural approach at mitigating complications associated with diabetes, although additional research is required to confirm these findings.
Date Created
2021-04-16
Agent

Assessing the relationship between cobalamin deficiency and methylation capacity in a vegetarian population

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Description
According to a 2016 census, eight million adults conform to a vegetarian diet within the United States, and about 50% of these adults follow a vegan diet. The census determined that plant-based diets are quickly growing in popularity particularly in

According to a 2016 census, eight million adults conform to a vegetarian diet within the United States, and about 50% of these adults follow a vegan diet. The census determined that plant-based diets are quickly growing in popularity particularly in young adults between the ages of 18 to 34 years. Many Americans are aware of the health benefits of a plant-based diet, however, the dietary risks associated with these diets are not well emphasized. Health concerns such as vitamin deficiencies and altered metabolism are heightened in vegetarian populations.

One Particular nutrient that is commonly lacking in the vegetarian diet is vitamin B12. Vitamin B12 is found mainly in animal-derived food sources such as meat, poultry, fish, dairy, and eggs. Although some vegetarians, called lacto-ovo vegetarians, consume dairy and eggs, vegans do not consume any animal products at all. Vitamin B12 deficiency can have devastating consequences on the human body due to its role as a methylation cofactor. Metabolism, DNA replication, and cancer formation all involve methylation processes.

This cross-sectional, differential study aimed to further understand the relationship between vegetarianism, vitamin B12 status, and methylation capacity in healthy adults. A group of 34 healthy adults (18 vegetarians and 16 omnivores) was recruited to analyze serum B12, homocysteine, methylmalonic acid, serum total folate, and transcobalamin II status. It was hypothesized that (1) vegetarians would have a lower vitamin B12 status, and thus, a lower methylation capacity than omnivores and that (2) low vitamin B12 status would be correlated with low methylation capacity.

The data show that vegetarians did not have significantly lower vitamin B12 methylation capacity status than omnivores. Nor was vitamin B12 status correlated with methylation capacity. However, the data revealed that diet quality had a positive influence on folate status. There was also a statistical trend (p=0.08) for homocysteine reduction in participants consuming high-quality diets. The data herein suggest that methylation capacity may be impacted by the quality of diet rather than the type of diet.
Date Created
2019
Agent

Effects of Menthol on Weight Regain and Maintenance of Caloric Restriction: A Pilot Study

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Description
The prevalence of excessive weight gain (obesity) has steadily increased since about 1980. Excessive weight gain is associated with many comorbidities; thus, a successful treatment is needed. The most common form of non-surgical treatment for excessive weight gain is caloric

The prevalence of excessive weight gain (obesity) has steadily increased since about 1980. Excessive weight gain is associated with many comorbidities; thus, a successful treatment is needed. The most common form of non-surgical treatment for excessive weight gain is caloric restriction with the intent to reduce body weight by 10%. Though this treatment is successful at reducing body weight, it often fails at maintaining the weight loss. Dietary menthol has been suggested as a possible treatment for excessive weight gain and has produced promising results as a preventative method for excessive weight gain. Our studies aimed at reducing weight regain and maintaining caloric restriction by feeding male Sprague-Dawley rats 0.5% dietary menthol during a period of caloric restriction, aimed at reducing their body weight by 10%, following an experimental period where the rats were fed a high-fat diet (HFD) or low-fat diet (LFD). The effects of the dietary menthol were observed during the weight regain period following the caloric restriction period. Two studies were conducted, and both were unable to achieve a maintenance of weight loss following caloric restriction, although our first study was able to produce a delay in weight regain and did not show any evidence of increased thermogenesis in menthol-treated rats. Our findings differ from the findings of previous studies on dietary menthol which could possibly be due to species effects, differences in procedures, age effects, or effects of different fatty acid compositions. The contrasting results in our studies could be due to genetic differences between litters used or a difference in manufacturing of the menthol diet between studies. Given the partial response to menthol in the first study, it can be suggested that the concentration of 0.5% may be below the threshold of menthol sensitivity for some rats. Future research should focus on increasing the concentration of dietary menthol from 0.5% to 1%, since the current concentration did not yield a reduction in weight regain or maintenance of caloric restriction.
Date Created
2019-05
Agent

Novel Organometallic Complex Mitigates Liver Injury caused by a 10-Week High Fat Diet in Adolescent Male Sprague-Dawley Rats

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Description
Nonalcoholic fatty liver disease is the most common form of chronic liver disease in the United States. Diets high in saturated fats are known to promote obesity and hepatic steatosis. The consumption of a high fat diet (HFD) can increase

Nonalcoholic fatty liver disease is the most common form of chronic liver disease in the United States. Diets high in saturated fats are known to promote obesity and hepatic steatosis. The consumption of a high fat diet (HFD) can increase the risk factors associated with insulin resistance, which can lead to the onset of diabetes and obesity. A prior study of a soil-derived organometallic complex (OMC) showed that supplementation reduces glucose and body mass in diabetic mice. The goal of this study was to test the efficacy of a similar OMC compound on the mitigation of hepatic steatosis induced from a HFD. Six-week-old male Sprague-Dawley rats (n=42) were divided into the following diet groups: standard rodent chow or 60% kcal from fat high fat diet (mainly lard) for 10-weeks. Rats were further divided into OMC treatment groups with OMC added to their drinking water: 0 mg/ml, 0.6 mg/ml or 3.0mg/ml OMC. At 10 weeks, study animals were euthanized with sodium pentobarbital (200 mg/kg, i.p.) and cardiac plasma as well as liver samples were collected and stored at -80° C until further analyses. Plasma ALT and AST as well as liver triglyceride and free glycerol concentrations were measured using commercially available kits. To assess cellular injury, aspartate transaminase (AST; released mainly from injured cardiac and liver cells) and alanine transaminase (ALT; released mainly from injured liver cells) were examined. Rats fed HFD had elevated plasma ALT activity, which was prevented by treatment with the high dose of OMC (p<0.05). No changes in plasma AST activity were detected. Examination of liver triglyceride and free glycerol concentrations showed increased fat accumulation in the liver of rats consuming HFD (Two-Way ANOVA, p<0.001). OMC did not prevent this increase. These findings suggest that, although OMC does not prevent the accumulation of lipids in the liver of rats fed HFD, it does mitigate liver injury resulting from excess dietary intake of saturated fats.
Date Created
2019-05
Agent

Hypoxia plus Glucose Deprivation Increases NF-κB Activation and Downstream Pro-Inflammatory Enzyme Levels in Human Brain Vascular Smooth Muscle Cells

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Description
Vascular inflammation is a key component for cerebrovascular disease and ischemic injury is suggested to be a significant contributor, resulting in either myocardial ischemia or stroke. A strong inflammatory response is characterized by the release of inflammatory cytokines, thus producing

Vascular inflammation is a key component for cerebrovascular disease and ischemic injury is suggested to be a significant contributor, resulting in either myocardial ischemia or stroke. A strong inflammatory response is characterized by the release of inflammatory cytokines, thus producing and/or activating pro-inflammatory proteins in the cell. Our previous studies have demonstrated that hypoxia plus glucose deprivation (HGD), an in vitro model of ischemia, increases the proinflammatory mediator, cyclooxygenase-2 levels (COX-2), in vascular tissues. Nuclear factor kappa B (NF-κB) activation is an upstream transcription factor of COX-2 and had been suggested to be involved in “sterile” inflammation in experimental stroke models. Mechanisms underlying the development and progression of inflammation in the cerebrovasculature following ischemic injury in human tissue has not been addressed. Thus, the purpose of this study was to examine the impact of HGD on NF-κB expression and activation in human brain vascular smooth muscle cells (HBVSMC). In addition, we assessed pro-inflammatory mediator levels of downstream NF-κB transcription products, COX-2 and iNOS, and level of its upstream receptor, TLR4. Primary HBVSMC at passage 7 were treated with normoxia (room air) or HGD (1% O2). Following exposure to HGD (3h), cells were isolated, homogenized, and total protein content determined. Lysates, either whole cell or nuclear and cytosolic fractions, were prepped for western blot and analysis. Anti-α-smooth muscle actin was used to verify HBVSMC origin and -actin was used as a loading control. NF-κBp65, phosphorylated NF-κBp65, COX-2, and TLR4 protein levels were all measured post HGD. NF-κBp65 total protein was expressed in HBVSMC and a trend for an increase in levels following HGD was observed. Indirect activation of pNF-kBp65 was assessed via nuclear fractionation studies and was increased following HGD. Lamin AC was used to verify nuclear fractionation. Additional findings suggested that HBVSMC expressed TLR4 however, total protein levels of TLR4 were not altered by HGD. COX-2 and iNOS protein levels were also increased following HGD. In conclusion, these studies indicate that HGD alters proinflammatory enzyme levels, potentially by altering NF-κBp65 activation in human vascular smooth muscle cells. Funding Support: University of Arizona Sarver Heart Center and University of Arizona Valley Research Project Grant VRP P1 (RG).
Date Created
2018-12
Agent

Examination of an Organometallic Complex on Insulin Resistance in Periadolescent Male Rats Following a 10-week High Fat Diet

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Description
With the rising prevalence of obesity and diabetes, novel treatments to help mitigate or prevent symptoms of these conditions are warranted. Prior studies have shown that fossilized plant materials found in soil lowers blood sugar in a mouse model of

With the rising prevalence of obesity and diabetes, novel treatments to help mitigate or prevent symptoms of these conditions are warranted. Prior studies have shown that fossilized plant materials found in soil lowers blood sugar in a mouse model of diabetes. The goal of this study is to determine whether a similar organometallic complex (OMC) could prevent insulin resistance in the skeletal muscle brought on by chronic high fat intake by examining the protein expression of key enzymes in the insulin signaling pathway and examining glucoregulatory measures. Six-week-old periadolescent male Sprague-Dawley rats (n=42) were randomly chosen to be fed either a high fat diet (HFD) (20% protein, 20% carbohydrates [6.8% sucrose], 60% fat) or a standard chow diet (18.9% protein, 57.33% carbohydrates, 5% fat) for 10 weeks. Rats from each diet group were then randomly assigned to one of three doses of OMC (0, 0.6, 3.0 mg/mL), which was added to their drinking water and fasting blood glucose was measured at baseline and again at 10 weeks. After 10 weeks, rats were euthanized, and soleus muscle samples were isolated, snap-frozen, and stored at -80°C until analyses. Fasting plasma glucose was measured using a commercially available glucose oxidase kit. Following 6 and 10 weeks, HFD rats developed significant hyperglycemia (p<0.001 and p=0.025) compared to chow controls which was prevented by high dose OMC (p=0.021). After 10 weeks, there were significant differences in fasting serum insulin between diets (p=0.009) where levels were higher in HFD rats. No significant difference was seen in p-PI3K expression between groups. These results suggest that OMC could prevent insulin resistance by reducing hyperglycemia. Further studies are needed to characterize the effects of diet and OMC on the insulin signaling pathway in skeletal muscle, the main site of postprandial glucose disposal. This study was supported by a grant from Isagenix International LLC as well as funds from Barrett, the Honors College at Arizona State University, Tempe Campus.
Date Created
2018-12
Agent

Consequences of Negative Energy Balance on Avian Reproductive Physiology: Endocrine and Metabolic Mediators

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Description
Reproduction is energetically costly and seasonal breeding has evolved to capitalize on predictable increases in food availability. The synchronization of breeding with periods of peak food availability is especially important for small birds, most of which do not store an

Reproduction is energetically costly and seasonal breeding has evolved to capitalize on predictable increases in food availability. The synchronization of breeding with periods of peak food availability is especially important for small birds, most of which do not store an extensive amount of energy. The annual change in photoperiod is the primary environmental cue regulating reproductive development, but must be integrated with supplementary cues relating to local energetic conditions. Photoperiodic regulation of the reproductive neuroendocrine system is well described in seasonally breeding birds, but the mechanisms that these animals use to integrate supplementary cues remain unclear. I hypothesized that (a) environmental cues that negatively affect energy balance inhibit reproductive development by acting at multiple levels along the reproductive endocrine axis including the hypothalamus (b) that the availability of metabolic fuels conveys alterations in energy balance to the reproductive system. I investigated these hypotheses in male house finches, Haemorhous mexicanus, caught in the wild and brought into captivity. I first experimentally reduced body condition through food restriction and found that gonadal development and function are inhibited and these changes are associated with changes in hypothalamic gonadotropin-releasing hormone (GnRH). I then investigated this neuroendocrine integration and found that finches maintain reproductive flexibility through modifying the release of accumulated GnRH stores in response to energetic conditions. Lastly, I investigated the role of metabolic fuels in coordinating reproductive responses under two different models of negative energy balance, decreased energy intake (food restriction) and increased energy expenditure (high temperatures). Exposure to high temperatures lowered body condition and reduced food intake. Reproductive development was inhibited under both energy challenges, and occurred with decreased gonadal gene expression of enzymes involved in steroid synthesis. Minor changes in fuel utilization occurred under food restriction but not high temperatures. My results support the hypothesis that negative energy balance inhibits reproductive development through multilevel effects on the hypothalamus and gonads. These studies are among the first to demonstrate a negative effect of high temperatures on reproductive development in a wild bird. Overall, the above findings provide important foundations for investigations into adaptive responses of breeding in energetically variable environments.
Date Created
2018
Agent

The Effects of Sumac on Saturated Fat-induced Inflammation in Human Vascular Smooth Muscle Cells and Isolated Mesenteric Arteries from Rats

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Description
Cardiovascular disease (CVD) is characterized by impaired vasodilation and the development of atherosclerosis.78 A diet high in saturated fat, such as palmitate, contributes to this by promoting inflammation and oxidative stress in human vascular smooth muscle cells (VSMC). 11,12,84,88 The

Cardiovascular disease (CVD) is characterized by impaired vasodilation and the development of atherosclerosis.78 A diet high in saturated fat, such as palmitate, contributes to this by promoting inflammation and oxidative stress in human vascular smooth muscle cells (VSMC). 11,12,84,88 The inflammation cascade that occurs increases pro-inflammatory cytokines, like tumor necrosis factor alpha (TNF-alpha) and increases proinflammatory enzymes like cyclooxygenase 2 (COX-2) contributing to inflammation, oxidative stress, blood pressure shifts, and atherosclerosis.11,12,69,84 Palmitate has been found to upregulate TNF-alpha,85 and COX-2. 11,12, 84

In various studies, sumac, a Mediterranean spice and known antioxidant,39,7,66,67 has been shown to have antioxidant properties through its ability to inhibit reactive oxygen species (ROS) such as superoxide.39,7,66,67 Sumac has also been found to reduce TNF-alpha.100 Results from a study of hypertensive human subjects fed a sumac supplement showed a decrease in blood pressure.59

In the current study, COX-2 levels were determined to evaluate the level of inflammation in response to palmitate when primary aortic human vascular smooth muscle cells (HAoVSM) were treated with sumac. The treatments included: vehicle (bovine serum albumin), 100 µM palmitate, and 10, 20, 40, 60, and 80 µg/mL sumac. Sumac did not alter COX-2 protein levels between vehicle and sumac groups. Additional studies were designed to examine whether 80 µg/mL sumac could reverse impaired vasodilation caused by 10 weeks of high fat intake, consisting of 60% of total calories from fat, in Sprague-Dawley rats. Mesenteric arteries were isolated and exposed to sumac. High fat diet (HFD) arteries had impaired vasodilation compared to arteries from chow-fed fats. HFD arteries exposed to sumac had similar endothelium-dependent vasodilation responses as those not exposed to sumac, however, there were trends for improved vasodilation. I suggest that sumac likely exhibits antioxidant capabilities that prevent superoxide from decreasing the bioavailability of nitric oxide in the vasculature, thus promoting endothelium-dependent vasodilation and preventing the creation of more harmful reactive oxygen species. Isolated arteries from chow fed rats developed irreversible vasodilation when exposed to sumac and were therefore not responsive to pre-constriction with phenylephrine (PE) likely related to nitrates and gallic acid naturally present in sumac whereby inhibiting PE.
Date Created
2018
Agent