Location: Dietary Prevention of Obesity-related Disease Research
2015 Annual Report
Objectives
Objective 1: Determine the effect of consuming dietary sources of fat with varied saturation and chain length on the physiological responses of satiety, lipid oxidation, and energy metabolism.
Sub-objective 1A: Determine the acute effects of consuming dietary fats of varied saturation and chain length on satiety, thermogenesis and energy utilization in healthy individuals.
Sub-objective 1B: Determine the chronic effects of consuming dietary fats of varied saturation and chain length on satiety, energy utilization, and body composition.
Objective 2: Determine the role of long chain omega 3 (LCn3) fatty acids in modulating the function of bone cells and the contribution of RANKL/RANK/OPG pathway in obesity-induced changes in bone metabolism in animal and cell models.
Sub-objective 2A1: Define the role of LCn3 in preventing adiposity-induced bone loss.
Sub-objective 2B: Define the optimal ratio of n6/n3 in improving bone quality and quantity in an obesity animal model.
Objective 3: Define the influences of dietary fatty acids and energy balance upon conversion of alpha-linolenic acid (ALA; 18:3n3) to LCn3.
Sub-Objective 3A: Determine the effects of saturated fatty acids (SFA) content upon mechanisms of ALA disposition under eucaloric conditions.
Sub-Objective 3B: Determine the effects of SFA content upon mechanisms of ALA disposition in rodents under hypercaloric conditions.
Objective 4: Define the extent to which consuming rainbow trout bred for elevated LCn3 content reduces CVD risk markers, such as platelet reactivity and related eicosanoids, in people.
Approach
Fat is an essential part of a healthy diet. However, the fatty acid compositions of dietary fats are often overlooked in designing healthy diets. Many Americans consume diets high in saturated fatty acids (SFA) and low in unsaturated fatty acids, including long-chain omega-3 fatty acids (LCn3). This imbalance may contribute to obesity and exacerbate osteoporosis and cardiovascular disease (CVD). The aim of our work is to provide robust data that will inform evidence-based recommendations for the appropriate levels and composition of dietary fats to maintain health and prevent disease. We will accomplish this aim by completing four research objectives that will clarify how the fatty acid profile of dietary fat contributes to health, or conversely, to disease progression. These objectives will use a combination of clinical translational studies in humans and mechanistic studies in rodents and isolated cells. Objective 1 addresses the role of dietary fats in the development of obesity by studying their effects on the modulation of satiety and energy metabolism; Objective 2 addresses the roles of specific fatty acids in preventing bone structure deterioration and promoting bone health in obesity; Objective 3 addresses the impacts of dietary fatty acids and energy balance on LCn3 metabolism; Objective 4 addresses the impact of consuming LCn3-rich rainbow trout on CVD risk markers in humans. We will fulfill these objectives through a combination of clinical translational and mechanistic studies involving human volunteers and rodent models.
Progress Report
Objective 1A. In this clinical trial we are evaluating the energetic and satiety responses to dietary fat intake in humans. Specifically, in an acute study, we are evaluating the responses to saturated fat, monounsaturated fat, and polyunsaturated fat containing high linoleic acid, high alpha-linolenic acid, or long chain omega-3 fatty acids. Participants are given a test meal and their energetic responses (energy expenditure, thermic effect of food, and beta-oxidation of fat) and satiety (gut hormones and subjective responses) are determined over 4 hours. The protocol has been developed and reviewed by Center scientists; Institutional Review Board (IRB) approval received; initiation of trial is underway. An amendment submitted to the IRB to add the determination of fatty acid binding protein polymorphisms to the study has been approved. These data will be used as a covariate in assessing responses.
Objective 1B. In this clinical trial we are evaluating the energetic and satiety responses to dietary fat intake in humans. Specifically, in a chronic feeding trial, we are evaluating the responses to saturated fat, monounsaturated fat, and polyunsaturated fat containing high linoleic acid, high alpha-linolenic acid, or long chain omega-3 fatty acids (LCn3). Participants will be given a 4 week dietary intervention after which their energetic responses (energy expenditure, thermic effect of food, and beta-oxidation of fat) and satiety (gut hormones and subjective responses) will be determined over 4 hours. We will determine fatty acid binding protein polymorphisms to be used as a covariate in assessing responses. The protocol has been developed and IRB approval is pending.
Objective 2. An animal study has been initiated to define the role of LCn3 in preventing adiposity-induced bone loss in mice. Sixty male C57BL/6 mice were assigned randomly to 6 treatment groups and fed either a 10% fat control diet or a 45% high-fat diet with three levels (0, 1, or 3%) of LCn3 from fish oil. Body weight, feed intake, and body composition were measured. Animals will be fed the experimental diets for 6 months and the study is expected to finish this year.
Objective 3. We tested whether the content of dietary saturated fatty acids, vs oleic acid, decreases the metabolism of alpha-linolenic acid (ALA) to longer n3 fatty acids. In adult mice, we found that animals fed a high-fat diet (but with equicaloric intake) with high oleic acid (from high oleic sunflower oil) actually decreases the levels of ALA in the liver as well as the level of the n3 metabolite eicosapentaenoic acid (EPA). The level of saturated fat increased the formation of long chain n3 fatty acids. These changes are reflected in differences in gene expression for proteins necessary for n3 metabolism. Results from this work are currently under preparation for publication.
We are repeating this study with younger mice to determine if there is an age component and with adult animals fed the diet a shorter length of time to determine if there is a time component.
Objective 4. In this clinical trial, we are comparing the efficacy of fish with differing long chain n3 fatty acid contents to reduce cardiovascular disease (CVD) risk markers in obese people with elevated CVD risk. Specifically, we are comparing diploid and triploid farm-raised rainbow trout and tilapia. To date, all fish have been obtained and the fatty acid profile determined. IRB approval has been obtained and we are actively recruiting for the study.
Accomplishments
1. Seafood Intake in the U.S. Do Americans meet dietary guidelines for seafood intake? ARS scientists at Grand Forks, ND, published an important analysis of current intake patterns of fish in the US evaluating the reported intake from the recent NHANES survey. These data showed that most individuals do not meet the intake level of fish recommended by the Dietary Guidelines for Americans. Intake is quite variable across the grouping evaluated. The researchers found that intake varies by income, education level, and sex but not by race-ethnicity. The data can inform public policy and educational efforts regarding fish intake.
2. Electronic methods of dietary assessment. What is the best way to assess dietary intake of participants and patients? ARS scientists at Grand Forks, ND performed a study of dietitian entry of food records compared to direct entry of diet records in electronic devices (computer, iPad) and demonstrated that electronic diet recording provides valid nutrient data for groups while the dietitian entry shows reduced variability which is better for individuals. These data will help clinicians and researchers who need to evaluate dietary intake.
3. Bone structure deterioration of obese rats can be improved by involuntary wheel running. Does exercise prevent bone loss resulting from obesity? ARS scientists at Grand Forks, ND investigated whether exercise affects bone structure and markers of bone metabolism in obese rats. They demonstrated that exercise decreased body fat but did not fully protect against the negative skeletal effects of existing obesity induced by a high-fat diet. These findings can be used to develop dietary and exercise strategies to improve bone health.
4. Peroxisome proliferator-activated receptor (PPAR) gamma plays a role in bone remodeling. Do bone marrow fat cells influence bone turnover? ARS scientists at Grand Forks, ND investigated how bone marrow fat cells affect the number and function of bone forming cells, osteoblasts, using a bone specific PPAR gamma conditional knockout animal model. They demonstrated that PPAR gamma increased the abundance of osteoblasts during bone remodeling. The findings will help understand how bone marrow fat cells affect bone metabolism.
5. Honey and high fructose corn syrup cause similar blood sugar responses. It is commonly believed that honey has different effects than other sugars. ARS scientists at Grand Forks, ND conducted a clinical trial and demonstrated equivalent glycemic response to chronic intake of honey, high fructose corn syrup, and sucrose in humans. Blood glucose and insulin responses were not different between the different sweeteners. Serum triglyceride levels were elevated after daily intake of 50g of all sugars for two weeks in all participants indicating that this level of intake has detrimental effects no matter what the sugar source is. These results add important knowledge regarding the metabolism of sugars in glucose tolerant and glucose intolerant individuals which may impact dietary guidance regarding sugar intake.
6. Obesity and antioxidants have separate effects on liver fatty acid metabolism. Obesity disrupts fatty acid metabolism in the liver and some studies suggest that antioxidants may benefit liver function by reducing oxidative stress. ARS scientists at Grand Forks, ND, determined that obesity and supplementation with vitamin C and vitamin E had separate effects upon the formation of oxidative fatty acid metabolites in the liver. These results further our knowledge of obesity biology and indicate that antioxidant supplementation may not alter the effects of obesity in the liver.
Review Publications
Troup, R., Hayes, J.H., Raatz, S.K., Thyagarajan, B., Khaliq, W., Jacobs, D.R., Key, N.S., Morawski, B.M., Kaiser, D., Bank, A.J., Gross, M. 2015. Effect of black tea intake on blood cholesterol concentrations in individuals with mild hypercholesterolemia: A diet-controlled randomized trial. Journal of the Academy of Nutrition and Dietetics. 115(2) 264-271.
Jahns, L.A., Raatz, S.K., Johnson, L.K., Kranz, S., Silverstein, J., Picklo, M.J. 2014. Intake of seafood in the U.S. varies by age, income, and education level but not by race-ethnicity. Nutrients. 6(12):6060-6075.
Raatz, S.K., Scheett, A.J., Johnson, L.K., Jahns, L.A. 2015. Validity of electronic diet recording nutrient estimates compared to dietitian analysis of diet records: A randomized controlled trial. Journal of Medical Internet Research. 17(1).
Raatz, S.K., Jahns, L.A., Johnson, L.K., Crosby, R.D., Mitchell, J.E., Crow, S.J., Peterson, C.B., Legrange, D., Wonderlich, S.A. 2015. Nutritional adequacy of dietary intake in women with anorexia nervosa. Nutrients. 7(5):3652-3665.
Raatz, S.K. 2014. Intensive lifestyle intervention reduces urinary incontinence in overweight/obese men with Type 2 diabetes: Results from the look AHEAD trial. Journal of Urology. 192:144-149.
Raatz, S.K. 2014. Evaluation of early weight loss thresholds for identifying nonresponders to an intensive lifestyle intervention. Obesity. 22(7):1608-1616.
Raatz, S.K. 2014. The look AHEAD trial: bone loss at four-year follow-up in type 2 diabetes. Diabetes Care. 37(10):2822-2829.
Yoneyama, S., Yiran, G., Lanktree, M.B., Barnes, M., Raatz, S.K. 2013. Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations. Human Molecular Genetics. 23(9):2498-2510.
Belalcazar, M.L., Anderson, A.M., Lang, W., Schwenke, D.C., Haffner, S.M., Raatz, S.K. 2014. Fiber intake and plasminogen activator inhibitor-1 in type 2 diabetes: Look AHEAD (Action for Health in Diabetes) Trial findings at baseline and 1 year. Journal of the Academy of Nutrition and Dietetics. 114(11):1800-1810.e2.
Raynor, H.A., Anderson, A., Miller, G.D., Reeves, R., Delahanty, L.M., Vitolins, M., Harper, P., Mobley, C., Konersman, K., Raatz, S.K. 2015. Partial meal replacement plan and quality of the diet at 1 year: Action for health in diabetes (Look AHEAD) trial. Journal of the Academy of Nutrition and Dietetics. 115(5):731-742.
Cao, J.J., Picklo, M.J. 2015. Involuntary wheel running decreases adiposity, improves but does not fully protect against negative skeletal effects of obesity induced by a high-fat diet in rats. Calcified Tissues International. 97(2):145-155.
Yuan, X., Cao, J.J., Liu, T., Li, Y., Scannapieco, F., He, X., Oursler, M.J., Zhang, X., Vacher, J., Li, C., Yang, S., Olson Olson, D. 2015. Regulators of G protein signaling 12 (Rgs12) promotes osteoclastogenesis in bone remodeling and pathologic bone loss. Cell Death and Differentiation. Available: http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd201545a.html.
White, D.K., Neogi, T., Rejeski, W., Walkup, M.P., Raatz, S.K. 2015. Can an intensive diet and exercise program prevent knee pain among overweight adults at high risk? Arthritis Care and Research. 67(7):965-971.
Espeland, M.A., Probstfield, J., Hire, D., Redmon, J., Raatz, S.K. 2015. Systolic blood pressure control among individuals with Type 2 Diabetes: A comparative effectiveness analysis of three interventions. American Journal of Hypertension. 28(8):995-1009.
Cao, J.J., Ou, G., Ding, K., Yang, N., Kream, B.E., Hamrick, M.W., Isales, C.M., Shi, X. 2015. Impact of targeted PPAR gamma disruption on bone remodeling. Bone. 410:27-34.
Yan, L., Graef, G.L., Nielsen, F.H., Johnson, L.K., Cao, J.J. 2015. Soy protein is beneficial but high-fat diet and voluntary running are detrimental to bone structure in mice. Nutrition Research. 35(6):523-531.
Zhou, Y., Mohan, A., Moore, D., Lin, L., Zhou, F.L., Cao, J.J., Wu, Q., Qin, Y., Reginato, A.M., Ehrlich, M.G., Yang, W. 2015. SHP2 regulates osteoclastogenesis by promoting preosteoclast fusion. Journal of Federation of American Societies for Experimental Biology. 29(5):1635-45.
Karl, J., Thompson, L.A., Niro, P.J., Margolis, L.M., Mcclung, J.P., Cao, J.J., Whigham Grendell, L.D., Combs, G.F., Young, A.J., Liberman, H.R., Pasiakos, S.M. 2014. Transient decrements in mood during energy deficit are independent of dietary protein-to-carbohydrate ratio. Physiology and Behavior. 139:524–531.
Picklo, M.J., Thyfault, J.P. 2015. Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats. Applied Physiology, Nutrition & Metabolism. 40(4):343-352.
Bukowski, M.R., Bucklin, C., Picklo, M.J. 2015. Quantitation of protein S-glutathionylation by liquid chromatograph-tandem mass spectrometry: Correction for contaminating glutathione and glutathione disulfide. Analytical Biochemistry. 469:54-64.
Raatz, S.K., Scheett, A.J., Johnson, L.K., Westereng, R.A., Langei, C.M. 2014. Community-based lifestyle intervention improves weight loss, fitness and chronic disease risk biomarkers. Journal of the Academy of Nutrition and Dietetics. 13(2):19-12.
