Excess adiposity is a risk factor for postmenopausal breast cancer and a major risk factor for recurrence in both pre- and postmenopausal breast cancer, and the biological mechanisms are not fully understood. Obesity is associated with elevated endogenous circulating estrogen as well as activation of the immune system, a key causative factor in insulin resistance and hyperinsulinemia. Optimal macronutrient distribution of weight loss diets has not been established. Cancer control guidelines have historically encouraged a lowfat diet, but current evidence does not suggest this strategy to be of particular benefit. Emerging evidence suggests that the optimal diet composition for weight loss may differ across individuals based on metabolic status and genetic factors. Effects of diet composition on hormonal and other factors linking obesity to breast cancer in weight loss interventions have not been compared or examined.
The specific aims ofthis study are: (1) To examine whether there is a differential weight loss response to different dietary macronutrient composition in a weight loss intervention in healthy obese women, depending on insulin resistance status; (2). To examine whether there is a differential response (depending on insulin resistance status) to different dietary macronutrient composition in a weight loss intervention in the hormonal factors and markers of inflammation that may link obesity to breast cancer mortality (insulin, SHBG, estrogens, C-reactive protein, interleukin-6 [IL-6], tumor necrosis factor a [TNF-a], and as a marker for gene expression, IL-6 and TNF-a gene methylation);and (3) To identify nutrient-gene interactions that contribute to differential response of cytokines to weight loss and diet composition associated with polymorphisms in IL-6 and TNF-a genes.
These aims will be addressed in a randomized controlled study involving 156 obese women randomly assigned to a high-carbohydrate (65% energy) low-fat (20% energy) or low-carbohydrate (45% energy) highmonounsaturated fat (35% energy) diet in a 12-month behavioral weight loss program. We hypothesize that greater weight loss and reduction in biomarkers will occur in insulin resistant women assigned to the lower carbohydrate, higher fat diet. We also hypothesize that the ability of weight loss and diet modification to decrease IL-6 and TNF-a concentrations will be influenced by polymorphisms in these genes. Results of this study will help to refine and individualize dietary guidance for optimal weight control and breast cancer prevention and will contribute to knowledge of mechanisms that link insulin resistance, inflammation and obesity to risk and progression of breast cancer.
Excess adiposity is a risk factor for postmenopausal breast cancer incidence and mortality, and it is a major risk factor for recurrence in both pre- and postmenopausal breast cancer. Optimal diet composition for weight loss may differ across individuals based on metabolic status. Results ofthis study will help to refine and individualize dietary guidance for optimal weight control and breast cancer prevention and will contribute to knowledge of mechanisms that link insulin resistance, inflammation and obesity to breast cancer.
|Kerr, Jacqueline; Patterson, Ruth E; Ellis, Katherine et al. (2016) Objective Assessment of Physical Activity: Classifiers for Public Health. Med Sci Sports Exerc 48:951-7|
|Le, Tran; Flatt, Shirley W; Natarajan, Loki et al. (2016) Effects of Diet Composition and Insulin Resistance Status on Plasma Lipid Levels in a Weight Loss Intervention in Women. J Am Heart Assoc 5:|
|James, Peter; Jankowska, Marta; Marx, Christine et al. (2016) ""Spatial Energetics"": Integrating Data From GPS, Accelerometry, and GIS to Address Obesity and Inactivity. Am J Prev Med 51:792-800|
|Fernandez, Marina O; Sharma, Shweta; Kim, Sun et al. (2016) Obese neuronal PPARÎ³ knock-out mice are leptin sensitive but show impaired glucose tolerance and fertility. Endocrinology :en20161818|
|Marinac, Catherine R; Nelson, Sandahl H; Breen, Caitlin I et al. (2016) Prolonged Nightly Fasting and Breast Cancer Prognosis. JAMA Oncol 2:1049-55|
|Schmitz, Kathryn H; Gehlert, Sarah; Patterson, Ruth E et al. (2016) TREC to WHERE? Transdisciplinary Research on Energetics and Cancer. Clin Cancer Res 22:1565-71|
|Chung, Heekyung; Chou, Winjet; Sears, Dorothy D et al. (2016) Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity. Metabolism 65:1743-1754|
|Patterson, Ruth E; Marinac, Catherine R; Natarajan, Loki et al. (2016) Recruitment strategies, design, and participant characteristics in a trial of weight-loss and metformin in breast cancer survivors. Contemp Clin Trials 47:64-71|
|Mitchell, Jonathan A; Godbole, Suneeta; Moran, Kevin et al. (2016) No Evidence of Reciprocal Associations between Daily Sleep and Physical Activity. Med Sci Sports Exerc 48:1950-6|
|Cho, Chang Gun; Pak, Kwang; Webster, Nicholas et al. (2016) Both canonical and non-canonical NF-ÎºB activation contribute to the proliferative response of the middle ear mucosa during bacterial infection. Innate Immun :|
Showing the most recent 10 out of 31 publications