Chow fed UC Davis strain female Lepr fatty Zucker rats exhibit mild glucose intolerance, hypertriglyceridemia, and increased urine volume, all reduced by a Brown Norway strain chromosome 1 congenic donor region.

Our objective is to identify genes that influence the development of any phenotypes of type 2 diabetes (T2D) or kidney disease in obese animals. We use the reproductively isolated UC Davis fatty Zucker strain rat model in which the defective chromosome 4 leptin receptor (LeprfaSte/faSte) results in fatty obesity. We previously produced a congenic strain with the distal half of chromosome 1 from the Brown Norway strain (BN) on a Zucker (ZUC) background (BN.ZUC-D1Rat183-D1Rat90). Previously published studies in males showed that the BN congenic donor region protects from some phenotypes of renal dysfunction and T2D. We now expand our studies to include females and expand phenotyping to gene expression. We performed diabetes and kidney disease phenotyping in chow-fed females of the BN.ZUC-D1Rat183-D1Rat90 congenic strain to determine the specific characteristics of the UC Davis model. Fatty LeprfaSte/faSte animals of both BN and ZUC genotype in the congenic donor region had prediabetic levels of fasting blood glucose and blood glucose 2 hours after a glucose tolerance test. We observed significant congenic strain chromosome 1 genotype effects of the BN donor region in fatty females that resulted in decreased food intake, urine volume, glucose area under the curve during glucose tolerance test, plasma triglyceride levels, and urine glucose excretion per day. In fatty females, there were significant congenic strain BN genotype effects on non-fasted plasma urea nitrogen, triglyceride, and creatinine. Congenic region genotype effects were observed by quantitative PCR of mRNA from the kidney for six genes, all located in the chromosome 1 BN donor region, with potential effects on T2D or kidney function. The results are consistent with the hypothesis that the BN genotype chromosome 1 congenic region influences traits of both type 2 diabetes and kidney function in fatty UC Davis ZUC females and that there are many positional candidate genes.

Locally harvested foods support serum 25-hydroxyvitamin D sufficiency in an indigenous population of Western Alaska.

BACKGROUND: Low serum vitamin D is associated with higher latitude, age, body fat percentage and low intake of fatty fish. Little documentation of vitamin D concentrations is available for Alaska Native populations. OBJECTIVE: This study was undertaken to investigate serum 25-hydroxyvitamin D (25(OH)D) concentrations of the Yup'ik people of southwestern Alaska in relation to demographic and lifestyle variables, particularly with the use of locally harvested (local) foods. DESIGN: Cross-sectional study. METHODS: We estimated 25(OH)D, dietary vitamin D and calcium, percent of energy from local foods and demographic variables in 497 Yup'ik people (43% males) aged 14-92 residing in southwestern Alaska. Sampling was approximately equally divided between synthesizing and non-synthesizing seasons, although the preponderance of samples were drawn during months of increasing daylight. RESULTS: Mean vitamin D intake was 15.1 ± 20.2 µg/d, while local foods accounted for 22.9 ± 17.1% of energy intake. The leading sources of vitamin D were local fish (90.1%) followed by market foods. Mean 25(OH)D concentration was 95.6 ± 40.7 nmol/L. Participants in the upper 50th percentile of 25(OH)D concentration tended to be older, male, of lower body mass index, sampled during the synthesizing season, and among the upper 50th percentile of local food use. CONCLUSIONS: A shift away from locally harvested foods will likely increase the risk for serum 25(OH)D insufficiency in this population.

Brown Norway chromosome 1 congenic reduces symptoms of renal disease in fatty Zucker rats.

We previously reported that a congenic rat with Brown Norway (BN) alleles on chromosome 1 reduces renal disease of 15-week old fatty Zucker rats (ZUC). Development of renal disease in fatty BN congenic and fatty ZUC rats from 9 through 28 weeks is now examined. Analysis of urine metabolites by (1)H nuclear magnetic resonance (NMR) spectroscopy revealed a significantly increased urinary loss of glucose, myo-inositol, urea, creatine, and valine in ZUC. Food intake was lower in the BN congenic rats at weeks 9-24, but they weighed significantly more at 28 weeks compared with the ZUC group. Fasting glucose was significantly higher in ZUC than congenic and adiponectin levels were significantly lower in ZUC, but there was no significant genotype effect on Insulin levels. Glucose tolerance tests exhibited no significant differences between ZUC and congenic when values were normalized to basal glucose levels. Quantitative PCR on livers revealed evidence for higher gluconeogenesis in congenics than ZUC at 9 weeks. Plasma urea nitrogen and creatinine were more than 2-fold higher in 28-week ZUC. Twelve urine protein markers of glomerular, proximal and distal tubule disease were assayed at three ages. Several proteins that indicate glomerular and proximal tubular disease increased with age in both congenic and ZUC. Epidermal growth factor (EGF) level, a marker whose levels decrease with distal tubule disease, was significantly higher in congenics. Quantitative histology of 28 week old animals revealed the most significant genotype effect was for tubular dilation and intratubular protein. The congenic donor region is protective of kidney disease, and effects on Type 2 diabetes are likely limited to fasting glucose and adiponectin. The loss of urea together with a small increase of food intake in ZUC support the hypothesis that nitrogen balance is altered in ZUC from an early age.

Enculturation, perceived stress, and physical activity: implications for metabolic risk among the Yup'ik--the Center for Alaska Native Health Research Study.

OBJECTIVES: American Indians and Alaska Natives (ANs) report among the lowest levels of physical activity in the USA, but there is very little systematic research examining the determinants of physical activity patterns in these populations. This study investigated the relationships between enculturation (or cultural traditionality), psychosocial stress, and physical activity in a community-based sample of Yup'ik women and men living in rural AN communities. Associations between these variables and several metabolic risk factors were also examined. DESIGN: A sample of 488 Yup'ik participants (284 women and 204 men) from six villages in the Yukon-Kuskokwim Delta region completed a wellness survey and an array of physiological assessments [e.g., body mass index (BMI), blood pressure]. A subset of 179 participants also completed a 3-day pedometer assessment of physical activity. RESULTS: Multivariate linear regression models indicated that participants who were more enculturated (i.e., living more of a traditional lifestyle) and who experienced lower levels of psychosocial stress were significantly more physically active. In turn, both lower levels of psychosocial stress and higher levels of physical activity were associated with lower BMI, lower percent body fat, and lower waist circumference. CONCLUSIONS: Findings underscore the importance of gaining a culturally specific understanding of physical activity patterns in indigenous groups in order to inform effective health promotion strategies.

Dietary supplement users vary in attitudes and sources of dietary supplement information in East and West geographic regions: a cross-sectional study.

BACKGROUND: Over 50% of adults currently use dietary supplements (DS) but manufacturers do not have to prove the safety or efficacy of a DS before it is marketed. Therefore, consumers may be exposed to inaccurate DS information, may lack confidence in choosing appropriate DS and may seek advice for usage. The objective of this study was to examine trends in usage, attitudes, and sources of information regarding DS according to geographic location, demographic group, and lifestyle choices. METHODS: Eligible individuals completed a 10-item researcher-developed survey tool to determine DS use, sources of DS information, and DS-related knowledge and attitudes over the previous year. Healthy participants (637 individuals aged 21-75 years) from two population-based cohorts that had been recruited for lipoprotein assessment studies at Tufts University in Boston, Massachusetts and University of California at Davis. Outcome measures included participants' use, beliefs regarding essentiality of DS, confidence in choosing appropriate DS, and sources of information on DS. Univariate and multivariate logistic regression were utilized to examine differences in survey responses between groups. RESULTS: Of the total population 72.7% reported taking dietary supplements in the previous year. Those living on the West Coast (80.3%) had greater use than those living on the East Coast (60.7%). Those on the East Coast were more likely to believe DS were essential to health (48.7%) and to feel confident in choosing DS that were appropriate for them (51.0%). Overall, physicians were the most frequent source of DS information for more than 50% of participants on both coasts. CONCLUSION: Because DS usage is widespread, health care providers and nutrition educators must encourage patients to discuss their DS use and be equipped to provide information conducive to safe, efficacious consumption. Tailoring interventions for healthcare providers, media sources, industry, and the public may allow for dissemination of up-to-date information regarding DS.

Normal range of human dietary sodium intake: a perspective based on 24-hour urinary sodium excretion worldwide.

BACKGROUND: The recommendation to restrict dietary sodium for management of hypertensive cardiovascular disease assumes that sodium intake exceeds physiologic need, that it can be significantly reduced, and that the reduction can be maintained over time. In contrast, neuroscientists have identified neural circuits in vertebrate animals that regulate sodium appetite within a narrow physiologic range. This study further validates our previous report that sodium intake, consistent with the neuroscience, tracks within a narrow range, consistent over time and across cultures. METHODS: Peer-reviewed publications reporting 24-hour urinary sodium excretion (UNaV) in a defined population that were not included in our 2009 publication were identified from the medical literature. These datasets were combined with those in our previous report of worldwide dietary sodium consumption. RESULTS: The new data included 129 surveys, representing 50,060 participants. The mean value and range of 24-hour UNaV in each of these datasets were within 1 SD of our previous estimate. The combined mean and normal range of sodium intake of the 129 datasets were nearly identical to that we previously reported (mean = 158.3±22.5 vs. 162.4±22.4 mmol/d). Merging the previous and new datasets (n = 190) yielded sodium consumption of 159.4±22.3 mmol/d (range = 114-210 mmol/d; 2,622-4,830mg/d). CONCLUSIONS: Human sodium intake, as defined by 24-hour UNaV, is characterized by a narrow range that is remarkably reproducible over at least 5 decades and across 45 countries. As documented here, this range is determined by physiologic needs rather than environmental factors. Future guidelines should be based on this biologically determined range.

Efficacy and tolerability of an herbal formulation for weight management.

The clinical effects and tolerability of a novel herbal formulation comprising the extracts of Sphaeranthus indicus and Garcinia mangostana were assessed in two similarly designed randomized, double-blind, placebo-controlled, clinical trials in 100 human subjects with a body mass index (BMI) between 30 and 40 kg/m². Participants were randomized into two groups receiving either 400 mg of herbal blend twice daily or two identical placebo capsules. All subjects received three meals (2000 kcal/day) throughout the study and walked 5 days a week for 30 min. The primary outcome was reduction in body weight. Secondary outcomes were reduction in BMI and in waist and hip circumference. Serum glycemic, lipid, and adiponectin levels were also measured. Ninety-five subjects completed the trials, and data from these two studies were pooled and analyzed. At study conclusion (8 weeks), statistically significant reductions in body weight (5.2 kg; P<.0001), BMI (2.2 kg/m²; P<.0001), as well as waist (11.9 cm; P<.0001) and hip circumferences (6.3 cm; P=.0001) were observed in the herbal group compared with placebo. An increase in serum adiponectin concentration was also found in the herbal group versus placebo (P=.0008) at study conclusion along with reductions in fasting blood glucose (12.2%, P=.01), cholesterol (13.8%, P=.002), and triglyceride (41.6%, P<.0001) concentrations. No changes were seen across organ function panels, multiple vital signs, and no major adverse events were reported. The minor adverse events were equally distributed between the two groups. Our findings suggest that the herbal blend appears to be a well-tolerated and effective ingredient for weight management.

Leptin receptor interacts with rat chromosome 1 to regulate renal disease traits.

Linkage mapping in a backcross of {Brown Norway [BN/Crl (BN)] × ZUC-Lepr (faSte) (ZUC)} × ZUC identified a male-specific quantitative trait locus (QTL) for urinary albumin excretion (UAE) on rat chromosome 1. A homozygous ZUC.BN-(D1Rat42-D1Rat90)/Ste congenic was produced containing BN donor alleles from 135 to 276 Mb from chromosome 1 on the ZUC background. We observed threefold higher urinary albumin-to-creatinine ratios (ACR) in 15-wk-old Zucker background strain males than in same sex and age congenic animals when both strains are also homozygous for the ZUC leptin receptor fatty mutation (Lepr (faSte)) (P < 0.0001). We then linkage mapped within the donor region without confounded effects from other chromosomes. Phenotypes were collected in 248 F2 male rats in a population made by crossing parents heterozygous for both the BN donor region and ZUC Lepr (faSte). Significant interactions were observed between the Lepr genotype and chromosome 1 QTL for six renal traits: urine volume, UAE at 10 and 15 wk, ACR, right kidney weight, and plasma urea nitrogen. A few traits, such as UAE and ACR, exhibit a second peak at the distal end of the chromosome. Hydronephrosis exhibited one or two QTLs contingent on adjustment for body weight. The results now demonstrate at least two sets of coincident traits with different correlations to kidney function.

Genes unlinked to the leptin receptor influence urinary albumin excretion in obese Zucker rats.

We have previously shown that 90% of outbred obese Zucker Lepr(fa/fa) rats die prematurely of renal disease. Thus, renal disease in obese Zucker Lepr(fa/fa) rats may be caused by the LEPR mutation on chromosome 5, by the obesity, or it may be influenced by Zucker susceptibility alleles of genes on other chromosomes. We have searched for susceptibility genes on other chromosomes using urinary albumin excretion (UAE) as an early indicator of altered renal function in a backcross of (Brown Norway × inbred Zucker) F1 × inbred Zucker, which we name the BZZ cross. We killed 237 BZZ backcross animals at 15 wk of age. All included animals were homozygous for the fatty mutation of LEPR and were obese. Urinary creatinine measurements were used to calculate the albumin-to-creatinine ratio (ACR). We identified direct effect quantitative trait loci (QTLs) for UAE and ACR on chromosome 1 (LOD scores = 3.6 and 2.86, respectively) in males, and chromosome 4 (LOD score = 2.9) in females. Significant QTLs were identified for left kidney weight for females on chromosomes 3 and 12. We also demonstrated that kidneys from 15 wk old obese inbred Zucker rats already show evidence of kidney pathology: tubular dilation, proteinaceous fluid accumulation, evidence for inflammation, and mild mesangial and tubular membrane basement membrane thickening. Both lean Zucker rats and the Brown Norway rats showed no evidence for these changes. Thus, by removing the influence of the Lepr(fa/fa) mutation from analysis we have identified UAE QTLs unlinked to LEPR.

Effect of oral magnesium supplementation on measures of airway resistance and subjective assessment of asthma control and quality of life in men and women with mild to moderate asthma: a randomized placebo controlled trial.

BACKGROUND: Epidemiological data shows low dietary magnesium(Mg) may be related to incidence and progression of asthma. OBJECTIVE: To determine if long term(6.5 month) treatment with oral Mg would improve asthma control and increase serum measures of Mg status in men and women with mild-to-moderate asthma. SUBJECTS: 55 males and females aged 21 to 55 years with mild to moderate asthma according to the 2002 National Heart, Lung, and Blood Institute(NHLBI) and Asthma Education and Prevention Program(NAEPP) guidelines and who used only beta-agonists or inhaled corticosteroids(ICS) as asthma medications were enrolled. DESIGN: Subjects were randomly assigned to consume 340 mg(170 mg twice a day) of Mg or a placebo for 6.5 months. MEASUREMENTS: Multiple measures of Mg status including serum, erythrocyte, urine, dietary, ionized and IV Mg were measured. OBJECTIVE: markers of asthma control were: methacholine challenge test(MCCT) and pulmonary function test(PFT) results. Subjective validated questionnaires on asthma quality of life(AQLQ) and control(ACQ) were completed by participants. Markers of inflammation, including c-reactive protein(CRP) and exhaled nitric oxide(eNO) were determined. RESULTS: The concentration of methacholine required to cause a 20% drop in forced expiratory volume in in minute(FEV(1)) increased significantly from baseline to month 6 within the Mg group. Peak expiratory flow rate(PEFR) showed a 5.8% predicted improvement over time(P = 0.03) in those consuming the Mg. There was significant improvement in AQLQ mean score units(P < 0.01) and in overall ACQ score only in the Mg group(P = 0.05) after 6.5 months of supplementation. Despite these improvements, there were no significant changes in any of the markers of Mg status. CONCLUSION: Adults who received oral Mg supplements showed improvement in objective measures of bronchial reactivity to methacholine and PEFR and in subjective measures of asthma control and quality of life.

Westernizing diets influence fat intake, red blood cell fatty acid composition, and health in remote Alaskan Native communities in the center for Alaska Native health study.

OBJECTIVE: To investigate the impact of a Westernizing diet on fat intake, red blood cell fatty acid composition, and health risks among Yup'ik Eskimos living in rural Alaskan Native communities. DESIGN: Diet data and blood specimens were collected from 530 Yup'ik Eskimos aged 14 to 94 years old. Height, weight, and waist circumference were measured. STATISTICAL ANALYSES: Comparisons of select fatty acid intake between participants in quintiles of traditional food intake (percent energy) were made using analyses of variance and post hoc Bonferroni tests. General linear models were used to determine the association between traditional food intake and health outcomes. RESULTS: Fatty acid composition of the diet differed according to the level of traditional food intake. Traditional food intake was positively associated with higher total fat, eicosapentaenoic acid, and docosahexaenoic acid intake. No association was observed between traditional food intake and saturated fatty acid intake; indeed, participants consuming more traditional foods derived a substantially smaller proportion of their dietary fatty acids from saturated fatty acids (P<0.001). Analyses of red blood cell fatty acid composition supported these findings. After multivariable adjustment, traditional food intake was significantly positively associated with high-density lipoprotein cholesterol concentration and significantly negatively associated with triglyceride concentration (P<0.001). CONCLUSIONS: Diets emphasizing traditional Alaskan Native foods were associated with a fatty acid profile promoting greater cardiovascular health than diets emphasizing Western foods. Further research needs to evaluate the effects of a Westernizing diet on the overall diet of Alaskan Natives.

Nutrient intakes are associated with adherence to a traditional diet among Yup'ik Eskimos living in remote Alaska Native communities: the CANHR Study.

OBJECTIVES: To determine whether dietary westernization is associated with intake of select nutrients among Alaska Natives living in remote communities. To investigate participant characteristics associated with adherence to the traditional Alaska Native diet. STUDY DESIGN: Cross-sectional survey. METHODS: A 24-hour recall was collected from 241 men and 307 women aged 14-94 years living in seven remote communities of Western Alaska. Bivariate analyses and ANOVA were used to examine the relationship between energy from traditional foods (the primary variable of interest), participant characteristics and intake of select nutrients. RESULTS: Traditional foods accounted for 22% of energy intake.overall. This estimate varied by age, educational attainment, and geographic location. Participants in the highest quintile of traditional food intake consumed significantly more vitamin A, vitamin D, Vitamin E, Iron, and n-3 fatty acids than participants in the lowest quintile (p < 0.001). Intake of vitamin C, calcium, and total dietary fiber decreased with increased consumption of traditional foods (p < 0.001). CONCLUSIONS: The degree of dietary westernization contributes to nutrient intake, both positively and negatively, in a dose response manner. Participant characteristics, particularly age, must be addressed in the development of a nutrition education program since they are associated with distinct dietary intakes.

Multiple measures of magnesium status are comparable in mild asthma and control subjects.

Magnesium (Mg) may be a significant factor in asthma management. There is debate about how to best assess Mg status. We evaluated multiple indices of Mg status and lung function in 52 people with mild to moderate asthma and 47 controls. Mg measures included serum total, ionized and erythrocyte Mg, intravenous Mg load retention and dietary recall. Methacholine challenge and pulmonary function tests were used to assess diagnosis and severity of asthma. Mg status was similar in asthma and controls, and was not correlated to lung function. Total serum Mg closely reflected ionized Mg and offers a useful clinical diagnostic monitor.

Diet quality among Yup'ik Eskimos living in rural communities is low: the Center for Alaska Native Health Research Pilot Study.

OBJECTIVE: The objectives of this pilot study were to describe the nutrient intake of Yup'ik Eskimos in comparison with national intake, identify dietary sources of key nutrients, and assess the utility of the Healthy Eating Index (HEI) to measure diet quality of Yup'ik Eskimos living in rural Alaskan Native communities. PARTICIPANTS AND DESIGN: A single 24-hour recall was collected from 48 male and 44 female Yup'ik Eskimos (aged 14 to 81 years), who resided in three villages in the Yukon Kuskokwim River Delta, AK, during September 2003. MAIN OUTCOME MEASURES: HEI scores, nutrient intake, and traditional food intake. STATISTICAL ANALYSES PERFORMED: Spearman correlations for associations between variables. RESULTS: Youth scored higher than elders despite similar nutrient intakes. Overall diet quality was generally low; 63% of all participants' diets were classified as poor. Although the HEI serves to identify areas of concern with respect to diet quality, it is limited in its ability to detect the positive value of traditional foods. CONCLUSIONS: Traditional foods and healthful market foods, including rich sources of fiber and calcium, should be encouraged. Although traditional foods were important sources of energy and nutrients, market foods composed the preponderance of the diet, emphasizing the importance of appropriately modifying a diet quality index based on a Western framework, such as the HEI.

Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss.

Obesity is becoming a global epidemic in both children and adults, and it is associated with numerous co-morbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, is an independent risk factor for CVD and CVD risks have been also documented in obese children, and is associated with reduced life expectancy. A variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amount. As a whole, overweight/obesity predispose or is associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death through its impact on the cardiovascular system.

Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism.

Obesity is becoming a global epidemic in both children and adults. It is associated with numerous comorbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, obesity is an independent risk factor for CVD, and CVD risks have also been documented in obese children. Obesity is associated with an increased risk of morbidity and mortality as well as reduced life expectancy. Health service use and medical costs associated with obesity and related diseases have risen dramatically and are expected to continue to rise. Besides an altered metabolic profile, a variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amounts, even in the absence of comorbidities. Hence, obesity may affect the heart through its influence on known risk factors such as dyslipidemia, hypertension, glucose intolerance, inflammatory markers, obstructive sleep apnea/hypoventilation, and the prothrombotic state, in addition to as-yet-unrecognized mechanisms. On the whole, overweight and obesity predispose to or are associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death because of their impact on the cardiovascular system. The pathophysiology of these entities that are linked to obesity will be discussed. However, the cardiovascular clinical evaluation of obese patients may be limited because of the morphology of the individual. In this statement, we review the available evidence of the impact of obesity on CVD with emphasis on the evaluation of cardiac structure and function in obese patients and the effect of weight loss on the cardiovascular system.