Location: Obesity and Metabolism Research2010 Annual Report
1a. Objectives (from AD-416)
The overall goal of the proposed research is to identify foods, nutrients, and food components that promote health and prevent disease in at-risk populations; where possible diet-gene interactions will be explored. Over the next 5 years we will focus on the following objectives: OBJECTIVE 1: Determine the effects of specific foods, fortified foods, and nutrients on bone health of at-risk population groups. Sub-objective 1.A. Determine the effects of carbonated beverages and milk on calcium kinetics and calcium efflux from the skeleton of women and girls (Van Loan, Allen, and Huang). Sub-objective 1.B. Determine the effects of vitamin B12 deficiency on markers of calcium kinetics, bone health, and calcium metabolism in postmenopausal women (Allen, Van Loan). OBJECTIVE 2: Investigate vitamin B12 and zinc intestinal absorption and metabolism in at-risk populations. Sub-objective 2.A. Determine the absorption of 14C-vitamin B12 from fortified foods in elderly with gastric atrophy and H. pylori infection, pre- and post H. pylori treatment (Allen, Huang). Sub-objective 2.B. Determine the impact of SNPs in a major Zn uptake gene (ZIP4) on dietary Zn absorption using ZIP4-expressing cell lines. (Huang, Allen). OBJECTIVE 3. Investigate the effect of Zn supplementation on the development of prostate cancer, a cancer common in African-Americans, using a mouse prostate cancer model (TRAMP) (Huang).
1b. Approach (from AD-416)
The overall goal is to identify foods, nutrients, and food components that promote health and prevent disease in at-risk populations and to identify diet gene interactions where possible. To achieve this goal, human studies will be conducted investigating the effects of carbonated beverages and milk on calcium kinetics and calcium efflux from the skeleton of women and girls; effects of vitamin B12 deficiency on markers of calcium kinetics, bone health, and calcium metabolism in postmenopausal women; and determine the absorption of 14C-vitamin B12 from fortified foods in elderly with gastric atrophy and H. pylori infection, pre- and post H. pylori treatment. Animal models will be used to investigate the impact of SNPs in a major Zn uptake gene (ZIP4) on dietary Zn absorption using ZIP4-expressing cell lines and to investigate the effect of Zn supplementation on the development of prostate cancer, common in African-American men. There is a need to devise effective nutrition interventions to prevent the progress of chronic disease in at-risk populations. Replacing: 5306-51520-006-00D (Van Loan, Allen) and 5306-51530-014-00D (Huang). Formerly 5306-51520-006-00D (4/09).
3. Progress Report
The Effect of Dairy Foods on fat & weight loss examined efficacy of dairy foods to reduce weight, body fat, and inflammation while improving satiety and appetite control in overweight and obese adults. Inclusion of 3-4 servings of dairy/day did not result in greater weight or fat loss or more intra-abdominal adipose tissue loss compared to the low dairy group. Inflammatory markers did not change with 3-4 servings of dairy in the diet. Dairy foods did lead to significant improvement in vitamin D status and hormones regulating appetite demonstrated an effect of the dairy treatment over time with lower caloric intake at a buffet meal; suggesting appetite regulation with dairy foods results in better weight control. The primary manuscript has been submitted to co-authors for review. Effects of Vitamin B12 Deficiency on Markers of Calcium Kinetics had 3 women complete the full protocol. Absorption of 14C-Vitamin B12 from Fortified Foods in Elderly with Gastric Atrophy and H. Pylori Infection, Pre- and Post H. Pylori Treatment continues to encounter difficulty recruiting volunteers; 5 control subjects are complete, but no subjects with gastric atrophy have been enrolled. Several studies have been designed to examine improvement in nutritional status of individuals following dietary or supplemental interventions. These studies include: Effect of Animal Source Foods on Vitamin and Mineral Status in Kenya continues to evaluate micronutrient status in Kenyan women and their children; Vitamin and Mineral Supplementation in Children investigates effect of vitamin and mineral supplementation in children in rural Honduras; Vitamin B12 Supplementation in Elderly Chileans is determining benefits of vitamin B12 supplements or vitamin B12 fortified milk for neurological and cognitive function; and Lipid-Based Micronutrient Supplement for Infants and Lactating Women examines improvement of vitamin and mineral status in lactating women and their infants given a micronutrient-rich lipid-based supplement. The Impact of SNPs in a Major Zn uptake Gene (ZIP4) on dietary Zn absorption using ZIP4-expressing cell lines has been studied using glycosylation, trafficking, and degradation assays. Data analysis and manuscript submission were accomplished. The study demonstrated that single nucleotide polymorphisms (SNPs; single changes in the genetic code that alter ZIP4 protein) did not change the rate of zinc uptake in yeast and human cell models. This study indicates that while ZIP4 sequences differ across the population, known changes in the sequence do not appear important to regulating zinc homeostasis. The effect of Zn supplementation on the development of prostate cancer has shown in mice that a mutation of the zinc transporter protein Znt7-null promotes prostate cancer progression. Early onset of prostate cancer and aggressive progression of the prostate cancer seen in TRAMP/Znt7-/- mice were due to the combination of increased cell proliferation and decreased cell apoptosis of Tag-expressing epithelial cells in the prostate of TRAMP/Znt7-/- mice. Results highlight the importance of maintaining normal prostate tissue zinc status to thwart cancer progression.
1. Effect of Dairy Foods on Fat and Weight Loss With Moderate Energy Restriction in Overweight and Obese Adults: Researchers at Davis, CA examined the role of dairy foods to enhance central fat and weight loss in overweight and obese adults who received a weight loss diet with either low or adequate servings of dairy foods. Measures of body weight, body composition, intra-abdominal adipose tissue (IAAT), adipose cell size, macrophage number in adipose tissue, and blood markers of energy and appetite regulating hormones were made at the start and end of a 12-wk intervention. We found a significant loss in body weight, body fat and IAAT over time, but no added effect with the added dairy servings. Adipose cell size and inflammation did not change over time. However, dairy foods led to a significant improvement in vitamin D status. Consuming 3-4 servings of dairy foods per day for 12 weeks lowered food intake during a buffet meal. These results suggest that dairy foods may have an impact on appetite control.
2. Znt7-null mutation promotes prostate cancer progression in TRAMP mice: Studies using human prostate cell lines suggested that a decrease in cellular zinc accumulation in prostate epithelial cells is associated with tumorigenic process through down-regulation of apoptosis. To test whether the genetic depletion of the zinc transporter ZnT7 expression would affect prostate cancer development and to elucidate molecular mechanisms underlying the effect of cellular zinc depletion on tumor growth, mice carrying both TRAMP and the null-Znt7 mutation in their genome were generated. The study suggests that a disruption/dysregulation of cellular zinc homeostasis in the epithelium of the prostate is highly associated with the tumorigenesis/transformation process of the cell. This pioneering work revealed basic mechanisms by which zinc homeostasis affects oncogene and tumor suppressor gene expression. This in vivo animal work sets a foundation for future research to understand how changes in cellular zinc homeostasis affects prostate cancer onset and development in humans.Allen, L.H. 2009. How common is vitamin B12 deficiency? American Journal of Clinical Nutrition. 89:693S-696S.