<div> <div> <div> <p>Incidence rates of adolescents with type 2 diabetes are increasing rapidly; there was an increase of 30% between 2019 and 2009. Even more alarming is that studies show that the most effective treatment, metformin monotherapy, is only effective at maintaining glycemic control in approximately 50% of individuals. Additionally, adolescents with diabetes may experience serious microvascular and macrovascular complications sooner than adults, which can impact the quality of life of young adults across the globe. Therefore, diabetes in adolescents is a public health concern, and there is very little research to guide treatment and prevention. It is widely known that adolescents have a very poor dietary pattern, characterized by increased intakes of added sugars from refined grains, and minimal amounts of fruits, vegetables, and fiber. There is conflicting evidence in the literature connecting increased added sugar intake to insulin resistance and diabetes development. Considering the very poor diets consumed by adolescents, and that nutrition is a modifiable risk factor for diabetes, we aimed to examine the associations between added sugar consumption, glycemic values, and measures of insulin resistance and beta-cell function. This pilot study analyzed dietary and glycemic data from participants that were screened for an ongoing randomized control trial which is an adolescent diabetes prevention program that uses health coaching to improve diet and physical activity behaviors called the Dietary Intervention for Glucose Tolerance in Teens (Dig It) Study. Fasting blood glucose, glycated hemoglobin (HbA1c), and 2-hour glucose concentrations were collected during an oral glucose tolerance test that was used to screen adolescents with obesity for diabetes. Consumption of added sugar and other dietary intake data were collected from food records created by the Technology Assisted Dietary Assessment (TADA) application. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin concentrations in the fasting state (1) obtained from an oral glucose tolerance test (OGTT). Whole-body insulin sensitivity index (WBISI), and the oral disposition index (DI) were calculated from measures obtained during oral glucose tolerance testing(2, 3)</p></div></div></div><div><div><div><p> Statistical analysis was performed using SPSS software and included independent t-tests and Pearson correlations. Of the 48 participants included in this analysis, 59.2% were female, 32% were African American, 57% were white, and 8.2% were more than one race. The mean age was 16.20 ± 2.7 years, and 42% had prediabetes. Those with normoglycemia consumed 11.0 ± 5.1% of energy from added sugars, compared to 9.4±5.1% energy from added sugars for individuals with prediabetes. There was no significant correlation between HbA1c and percent calories coming from added sugar (R= -0.237, P=0.063), percent calories coming from added sugar and fasting blood glucose (R= 0.208, P= 0.090), or percent calories from added sugar and 2-hour glucose (R= 0.017, P= 0.457). There were no significant correlations found between percent calories from added sugar and HOMA-IR (R= 0.129, P= 0.234), percent calories from added sugar and WBISI (R= -0.069, P= 0.350), or percent calories from added sugar and DI (R= -0.118, P= 0.253). There were also no significant differences between the mean values of HbA1c, fasting glucose, or 2-hour glucose between individuals that consumed high vs. low amounts of added sugar, as measured by an independent t-test. The p-values were 0.634, 0.434, and 0.234 respectively. To examine the extent to which % calories from added sugar predicted variances in glycemic values, hierarchical multiple regression analyses were performed. Once energy, physical activity, BMI Z-Score, and age were entered into the model, % energy from added sugar accounted for an additional 9.6% variance in HbA1c. In conclusion, we did not find significant associations between consumption of added sugar and glycemic and insulin resistance or beta-cell function outcomes in adolescents who are obese, however our study lacked sufficient power. While our findings were not definitive, studies to identify dietary factors that promote or prevent hyperglycemia and insulin resistance are needed to inform dietary intervention strategies that may be effective at decreasing T2D in adolescents. </p> <p>12 </p> </div> </div> </div>

<p> Intestinal phosphorus absorption is a key contributor to the body phosphorus pool, but much is unknown regarding physiological adaptations in intestinal phosphorus absorption that occur in vivo. We sought to measure changes in intestinal phosphorus absorption efficiency and phosphorus balance in adolescent females and in rats in response to several factors, using physiologically relevant assessment approaches including whole-body phosphorus balance techniques and <i>in situ</i> ligated intestinal loop absorption methods.</p> <p> We first assessed phosphorus balance and net phosphorus absorption in female adolescents from a controlled crossover study with two levels of calcium intake. Despite an increased calcium intake of 600 mg/day, there was no change in phosphorus balance, nor a significant change in net phosphorus absorption.</p> <p> Next, we measured intestinal phosphorus absorption efficiency with the <i>in situ</i> ligated loop method in healthy Sprague Dawley rats as well as the Cy/+ rat model of progressive kidney disease. We found 10-week-old healthy rats had a small but higher absorption efficiency of phosphorus compared to 20- and 30-week-old rats, while 20-week Cy/+ rats had higher absorption efficiency than 30-week-old. Each of these results corresponded to net phosphorus absorption from balance as well as the concentration of 1,25-dihydroxyvitamin D3. In healthy rats, there was no effect of altering the level of phosphorus in the diet on absorption efficiency. In Cy/+ rats, kidney disease produced a small <i>increase</i> in absorption efficiency, contrary to the predicted decrease that would occur with lower 1,25-dihydroxyvitamin D3 observed in CKD. Gene expression of the major intestinal phosphate transporter, NaPi-2b, largely followed absorption patterns.</p> <p> The utility of the Cy/+ model is limited to males as females do not begin to show signs of progressive kidney decline until a much older age. Therefore, we sought to test whether ovariectomy would accelerate kidney disease in Cy/+ females, with the aim of establishing a postmenopausal model of progressive kidney disease. Our results show that kidney disease is not accelerated by ovariectomy in this rat strain, as measured by kidney weight and biochemistries including blood urea nitrogen, creatinine, creatinine clearance, and plasma phosphorus and calcium.</p> <p> Our results utilizing <i>in situ</i> absorption measures as well as net absorption of phosphorus suggest that some of the factors that are understood to influence the intestinal absorption of phosphorus do not have a significant influence in a physiological context.</p>

<p>Potassium is an essential nutrient, that has been labeled a shortfall nutrient by recent Dietary Guidelines for Americans Advisory Committees. Increases in potassium intake have been linked to improvements in cardiovascular and other metabolic health outcomes. Blood pressure (BP) has often been cited as the primary criterion for determining potassium requirements. Hypertension (HTN), or high BP, is a primary risk factor for cardiovascular disease and other circulatory diseases. Cardiovascular disease (CVD) is responsible for the 31% of deaths worldwide. Findings from the Agency for Healthcare Research and Quality report (which informed the recently released Dietary Reference Intakes for sodium (Na) and potassium) on potassium intake and chronic disease concluded, with a moderate strength of evidence, that increasing potassium intake decreases BP, particularly among those with HTN. Although, of the 18 randomized controlled trials assessed by the AHRQ, only 4 were dietary interventions, the rest involved potassium supplementation. Observational studies also show a consistent bone benefit with increased potassium rich fruit and vegetable intakes in cohorts spanning adolescents to the elderly. In clinical trials, higher potassium intakes through supplementation have been associated with reduced urinary calcium (Ca) excretion and improvement in Ca balance. Although, similar to BP, intervention trials assessing the impact of dietary potassium on bone are lacking. Controlled feeding studies looking specifically at increases in potassium from food are sparse, leaving a large knowledge gap in the field for a nutrient with an important potential health impact. In general, little is known about whole-body potassium retention, with the few studies conducted lacking consistency and rigor in methods and design. What potassium retention means in terms of adequacy, or how higher or lower retention may influence specific health outcomes is understudied and not well understood. </p> <p>Utilizing a randomized, cross-over, controlled feeding clinical study with complete metabolic balance measures, our research aims to begin filling these gaps, looking specifically at the effects of potassium intake via potato sources and a potassium supplement on BP and vascular outcomes, as well as how the source of potassium may influence potassium, Na and Ca whole-body balance. </p> <p>This dissertation will discuss the physiology of potassium intake, how this may affect potassium, Na, and Ca retention, and in turn what influence this has on vascular and bone related health outcomes. Overall the goal of this research is to address the question: What is the importance of dietary potassium, and how can it benefit cardiovascular and skeletal health?</p>

<div> <div> <div> <p>Saliva influences chemical and textural sensations, yet details on sources of individual variability for these phenomena are still lacking. In this project, we investigated fatty sensations, dietary habits, and saliva’s emulsifying properties. Through a remote tasting and spitting protocol, participants were asked to rate sensory properties of fatty candies with varying concentrations of added linoleic acid (LA) as well as discriminate among fatty candies with/without LA and high/low fat ranch dressings. Additionally, participants swished and expectorated an oil/water mixture, and the expectorated emulsion was visually analyzed. Dietary habits were also assessed by 3-day dietary recalls. </p> <p>Linear mixed model was used to analyze sensory response, diet, and spit data. Sensory ratings of fatty candies indicate differences based on successful completion of either discrimination tasks. People who passed either discrimination tests (N=26 passed LA; N=22 passed high/low fat tests) rated higher “Fattiness” for the highest LA concentration. In contrast, people who failed the tests (N=36 failed LA; N=40 failed high/low fat tests) rated higher “Bitterness” with the highest LA concentration. Importantly, only 7 individuals overlapped in these two groups who passed the discrimination tasks. Lower total fat intake and larger expectorated fat layer were associated with higher “Bitterness,” particularly among those who passed the LA discrimination test and those who failed the high/low fat test. Moreover, lower protein and greater carbohydrate intake seemed to associate with the greater formation and stability of oral emulsions, particularly in individuals who failed the high/low fat discrimination task. Other factors such as total fat intake, medication usage, and BMI were mixed. In conclusion, sensory experience of fatty candies may vary based on the ability of an individual to sense the LA or fat content, and saliva’s ability to emulsify fat into water may vary with diet. </p> </div> </div> </div>

<p>    </p> <p>In the United States, colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer mortality in men and women. Recent epidemiological evidence has shown that there’s been a steady increase in young onset CRC, underlying a continued need to understand mechanisms that may be contributing to its development. One risk factor that continues to persist and rise is obesity. Obesity is a multifaceted disease characterized by various metabolic and physiologic changes that influence tumorigenesis. Another component that is altered in obesity and has been shown to contribute to CRC is the gut microbiota. Obesity associated gut microbiota is different relative to a lean counterpart and has been linked poor colonic health, which can increase risk for CRC. Researchers have shown that intestinal tumorigenesis is worse in diet induced obesity but given other related conditions like chronic inflammation, the role of the gut microbiota in obesity associated CRC risk has not been adequately isolated. To address this gap and to further explore the role of diet in this relationship given its importance in driving obesity and impacting gut microbiota composition, we performed two studies. First, we assessed the role of obesity and/or two different obesogenic diets on gut microbiota composition and intestinal permeability. We hypothesized that diet and obesity would affect gut microbial community composition and that obese mice would have higher intestinal permeability relative to lean mice regardless of diet. Our results indicated that both diet and obesity were significant predictors and had varying effects on species richness and community structure of the gut microbiota and significantly enriched multiple bacterial taxa. Second, to isolate the role of obesity- and/or diet- influenced gut microbiota on CRC development, fecal microbial transplantation was performed by transferring the intestinal content from mice in the first study into recipient mice before chemical induction of CRC. We hypothesized that the gut microbiota from obese mice on obesogenic diets would promote CRC independent from the development of obesity. Our results indicated that gut microbiota shaped by the obesogenic diets was associated with worse colonic tumor measurements, while the differences in gut microbiota due to obesity or leanness did not affect CRC outcomes. Overall, we have demonstrated that diet and obesity have significant effects on gut microbial communities, but only dietary-induced gut microbial changes promote CRC. These results highlight the importance of understanding dietary effects on gut microbiota in CRC development which improves our ability to determine better strategies of prevention and treatment. </p>

The primary role of 1,25(OH)₂D and the vitamin D receptor (VDR) during growth is to mediate intestinal calcium (Ca) absorption by regulating the expression of genes (e.g., Trpv6, S100g) that control Ca fluxes through enterocyte. In contrast to the well-defined role during rapid growth, the understanding of 1,25(OH)₂D signaling in post-growth, mature adult or the elderly is poor. Some observational studies suggest intestinal 1,25(OH)₂D signaling is not important to Ca absorption and bone for mature adult. In the elderly, intestine develops resistance to 1,25(OH)₂D action which might be due to age-related reductions in intestinal VDR level. In addition, there is lack of evidence that directly tests the role of 1,25(OH)₂D action in the distal intestine post-growth. My dissertation research focuses on discovering the importance of 1,25(OH)₂D signaling from both the temporal and spatial perspectives. By using 4-month old, whole intestine or large intestine VDR knockout mice, we found that for mature mice, 1,25(OH)₂D signaling plays a minimal role in regulating Ca absorption and protecting bone mass when dietary Ca intake is adequate. In contrast, 1,25(OH)₂D signaling in the whole intestine, and to a lesser extent the proximal colon, is critical to upregulate Ca absorption and protect bone when dietary Ca intake is low. Next, we proved that the Ca absorptive machinery in the proximal colon can be locally stimulated to enhance the expression of Trpv6 by 1,25(OH)₂D released from glycoside and glucuronide forms of calcitriol. Furthermore, our transcriptomic analysis on 1,25(OH)₂D-regulated genes in the duodenum of mature (4-month old), middle-aged (11.5-month old), and old (20.5-month old) mice suggest although aging did reduce the induction of some genes by 1,25(OH)₂D, this effect is not universally present across the genome and it is not related to intestinal Vdr expression. The findings from my dissertation research serve as a foundation for future research to identify a) the potential of specifically targeting proximal colon to increase intestinal Ca absorption and protect bone in adult; b) the molecular mechanisms that contribute to the aging-associated, non-universal resistance to 1,25(OH)₂D action.

Source: Masters Abstracts International, Volume: 45-06, page: 3137. Adviser: Jeanne B. Martin. Includes bibliographical references.

<div>Osteoporosis is the most common bone disease in older adults and is characterized by low bone mass and increased fragility. Women are at a higher risk for osteoporosis because of the rapid loss of bone during menopause. The decline of estrogen is accompanied by an increased bone resorption and a decreased bone formation which results in negative bone balance. Due to adverse effects on the uterus, breast and cardiovascular system, hormone replacement therapy has been discouraged. Nutritional strategies for osteoporosis prevention are being sought. It has been suggested that (poly)phenol-rich fruits may have bone protective effects. Blueberries are one of the richest sources of (poly)phenols, thus the aim of this dissertation was to determine whether a blueberry-enriched diet could aid in bone loss prevention in the ovariectomized rat model.</div><div><br></div><div>There are hundreds of blueberry varieties which differ in (poly)phenol profiles and content. Five blueberry varieties (Ira, Montgomery, SHF2B1-21:3, Onslow and Wild Blueberry) were chosen to assess the bioavailability of its individual (poly)phenols. Bioavailability of individual phenolic metabolites was determined through a pharmacokinetic study in ovariectomized rats. The results showed that Montgomery blueberry had significantly higher bioavailability of malvidin, cyanidin and myricetin metabolites, while Ira had significantly higher bioavailability of quercetin metabolites, thus suggesting that the absorption of blueberry polyphenols and their potential to reach target tissues differed between blueberry varieties.</div><div><br></div><div>It is important to assess what is the most appropriate dose of blueberry necessary to exert beneficial effects on bone. To determine the most adequate dose of wild blueberry to prevent bone loss in ovariectomized rats, a randomized crossover study was carried out to assess the effects of four different blueberry doses on net bone calcium retention over a 10-day treatment period. The results showed that the only dose to significantly increase net bone calcium retention by 25.6% (p = 0.0426) was the 5% blueberry diet (% w/w), while the higher doses of 10% and 15% had no effect on net bone calcium retention. This informed the last study where Montgomery blueberry and wild blueberry at a 5% dose (% w/w) were chosen to investigate the effects of an 8-week chronic feeding study on calcium metabolism, kinetics, bone microarchitecture and strength and polyphenol metabolism and distribution. A chronic consumption of the wild blueberry resulted in a trend towards minimal trabecular bone loss protection in comparison to the control diet (p=0.08). Kinetic modeling of calcium showed that the Montgomery blueberry had anabolic effects on bone through significantly increasing calcium absorption and bone deposition. The phenolic metabolism differed among blueberry varieties due to each berry’s polyphenol content and profiles and a chronic consumption of blueberry resulted in significant changes in absorption and metabolism of polyphenols. The bone marrow was investigated to determine whether there was any accumulation of phenolic acids in the tissue. Hippuric acid accumulation was significantly higher with the Montgomery blueberry treatments in comparison to control diet. Interestingly, hippuric acid content in the bone marrow was significantly and positively correlated with bone deposition calculated from kinetic modeling. Although no differences were observed on bone mineral density, strength, and microarchitecture, previous studies with a duration of 12-14 weeks have shown significant protection of a blueberry-enriched diet on bone mineral density. Because our study showed a trend for increased trabecular bone (p = 0.08) with the blueberry treatments, we conclude that an 8-week treatment was insufficient time to detect significant differences between the control and blueberry treatments. Since previous researchers before us have reported significant attenuation to bone loss immediately after OVX, it is possible that blueberry that in our study, blueberry was unable to rescue bone once lost after ovariectomy.<br></div><div><br></div><div>A blueberry-enriched diet resulted in a minimal protection to bone after stabilized to OVX, but showed significant increases in calcium absorption and bone turnover in ovariectomized rats. Colonic metabolite profiles from the chronic consumption of blueberry significantly changed over time, thus providing an insight into the effects of blueberry consumption on polyphenol metabolism.<br></div><div><br></div>

<div>As the soft tissue that transmits muscular forces to the bony skeleton, tendons play a key role in the human musculoskeletal system and must adapt over time to repeated mechanical loads to maintain functionality. Resistance exercise is one of the primary stimuli for increases in tendon size and strength in healthy, young individuals, but similar benefits are not observed in healthy, aged tendon. This failure in the elderly to adapt, along with the fact that tendons inevitably decline in morphology and function with age, puts older individuals at an increased risk of poor tendon health, subsequent injury, and a compromised quality of life. Alternative strategies to preserve and strengthen aged tendon has gone largely unexplored, highlighting a critical need to determine an effective stimulus for tendon adaptations in aging populations</div><div>The purpose of this study was to determine if age impacts the delivery of orally-consumed amino acids (AA) to the peritendinous Achilles space. If so, this investigation could serve as the foundation for future studies to evaluate the efficacy of supplemental amino acids for inducing positive adaptations in tendon during exercise. Furthermore, an enzyme-linked immunosorbent assay (ELISA) was performed to quantitively measure procollagen, a precursor of collagen, in the samples to evaluate the impact on supplemental amino acids on collagen synthesis. </div><div>To assess amino acid delivery, a microdialysis fiber was inserted into the peritendinous space anterior to the Achilles tendon in healthy young (n = 7, 21-30 years) and elderly (n = 6, 60-75 years) men and women after a twelve-hour fast. After baseline collection, subjects consumed a non-caloric, noncaffeinated AA beverage (16.65 g). Microdialysis samples were collected every fifteen minutes for four hours and analyzed using reverse-phase high-performance liquid chromatography. </div><div>Amino acid delivery to the peritendinous space was not compromised with age, and the administration of amino acids upregulated procollagen synthesis significantly more in healthy, elderly subjects than in those that are healthy and young. Though preliminary, these findings provide a strong foundation for future studies assessing the impact of amino acid supplementation as novel impetus for tendon adaptations in the elderly. </div><div><br></div>

<p>PUFAs serve many important biological and physiological functions within the body and are key for the structure and function of the brain. Omega-6 and omega-3 PUFAs are found in abundance in phospholipids of neuronal membranes that impart structure and function of neurons. Omega-6 PUFAs are instrumental for neurotransmission, neuronal elongation, and neuritogenesis; whereas, omega-3 PUFAs promote neuronal maturation through synaptogenesis. The types of PUFAs incorporated into neuronal membranes is especially important in determining the progression of development. The processes of neurogenesis, neuritogenesis and elongation require large amounts of PUFAs to be incorporated into the membrane phospholipids. To accommodate for the high PUFA needs, maternal dietary PUFA, especially EPA and DHA, recommendations, mobilization of fatty acids into maternal circulation increases, and the accretion rate of PUFA are increased. If maternal nutritional inadequacy of PUFAs occurs during gestation, this can result in impaired cognition, behavioral abnormalities, reduced number of neurons, decreased dendric arborization, altered myelin sheath, and a reduction in brain size. </p> <p> Even though the essentiality of PUFAs in neuronal development is widely accepted, the mechanism is not well understood. There is a lack of consensus in the current literature on the effects of individual PUFAs on each stage of neuronal development and the molecular pathways involved. Despite the inconsistent evidence, the results of numerous studies have consistently suggested that neuronal membrane PUFA composition is associated with neuronal development outcomes, such as number of neurons and neurites, neurite length, and neurotransmitter release. The varying results may be the result of methodological discrepancies with PUFA composition and concentrations, as well as the models used for neuronal development. Additionally, very few studies have taken into consideration the competitive relationship of omega-6 and omega-3 PUFAs in the body when assessing neurodevelopment. </p> <p> This thesis was focused on addressing the role of PUFAs in neuronal development and to address some of the inconsistencies in the literature. attempt to elucidate the individual roles of ALA, ARA, and EPA on neuronal membrane composition and neuronal development. The aim of the thesis research project was to assess the impact of individual PUFAs on neuronal membrane PUFA composition, the membrane n-6:n-3 ratio, and the morphology of SH-SY5Y cells during differentiation. The results of this study demonstrated that supplementation of individual PUFAs alters membrane PUFA composition and the n-6:n-3 ratio. However, there wasn’t a significant effect on neurite number with ALA, ARA, and EPA treatment. Lastly, ARA treatment decreased cell viability compared to the other treatments and the BSA control. Furthermore, additional research needs to be conducted to address other morphological measures and functional outcomes, such as neurotransmitter production and release.</p>