The proposed study will explore the pathogenesis of human obesity and overweight from a new angle - the possible effects of suspected industrial chemicals in a prospective study. While over-nutrition and sedentary lifestyle are well-established risk factors of obesity, a role of other potential obesity-contributing factors is highy likely and needs to be elucidated. Environmental chemicals known as """"""""obesogens"""""""" may upset body weight regulation. Perfluorinated compounds (PFCs) are ubiquitous, persistent chemicals that interfere with energy homeostasis in animal models. However, because of species-specific toxicokinetics, tissue distribution, and mechanisms of action of PFCs, the relevance of animal data to humans is uncertain. Human evidence originated primarily from cross-sectional studies is largely consistent with the hypothesis that PFCs are associated with higher body weight, but lack of prospective data precludes any causal inference. The investigators will, therefore, prospectively examine the roles of these pollutants in relation to human weight regulation in the well-designed and rigorously-implemented POUNDS LOST Trial that was recently completed. The participants of this 2-year trial consist of 811 men and women who were randomized to one of four calorie- reduced diets at baseline. While the diets had similar effects on weight change, substantial between-individual variability was observed in short-term weight-loss and subsequent weight-regain that cannot be explained by compliance or established obesity risk factors. The investigators will analyze banked plasma for PFCs to examine whether baseline PFC levels are associated with less weight-loss and greater weight-regain among ~700 participants who completed 6-month and 2-year follow-up. In addition, we will examine associations with waist circumference and fat content of whole body, abdomen, and liver that were longitudinally recorded in the trial. The investigators also aim to elucidate possible mechanisms by evaluating plasma PFC concentrations in regard to gene expression profiles in adipose tissue, as well as changes of adipokines and thyroid hormones. The multidisciplinary research team is comprised of experts with qualifications and experience in obesity research, environmental epidemiology, nutrition, genetics, and biostatistics, thus ensuring successful implementation of the current project. The prospective evidence will be directly relevant to humans, will likely lead to new insight and hypotheses regarding obesity and related disease outcomes, and will facilitate making more comprehensive and effective strategies for obesity prevention and treatment.

Public Health Relevance

Perfluorinated compounds (PFCs) are persistent chemicals that are known disruptors of energy homeostasis in animals and are, therefore, suspected of playing a role in human adipogenesis. The proposed investigation will utilize the rich data and resources in the POUNDS LOST Trial to prospectively examine human PFC exposure in relation to a wide array of outcomes, including weight loss, weight regain, and change of body fat distribution, adipokines, thyroid hormones, and gene expression profiles in adipose tissue, to determine the possible contribution by PFCs to adipogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES022981-01A1
Application #
8761806
Study Section
Kidney, Nutrition, Obesity and Diabetes Study Section (KNOD)
Program Officer
Heindel, Jerrold
Project Start
2014-07-01
Project End
2018-04-30
Budget Start
2014-07-01
Budget End
2015-04-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Harvard University
Department
Nutrition
Type
Schools of Public Health
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
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Sun, Qi; Zong, Geng; Valvi, Damaskini et al. (2018) Plasma Concentrations of Perfluoroalkyl Substances and Risk of Type 2 Diabetes: A Prospective Investigation among U.S. Women. Environ Health Perspect 126:037001
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Liu, Gang; Sun, Qi (2017) Response by Liu and Sun to Letter Regarding Article, ""Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality Among Men With Type 2 Diabetes: A 22-Year Prospective Study"". Arterioscler Thromb Vasc Biol 37:e57
Juan, Juan; Liu, Gang; Willett, Walter C et al. (2017) Whole Grain Consumption and Risk of Ischemic Stroke: Results From 2 Prospective Cohort Studies. Stroke 48:3203-3209
Zong, Geng; Gao, Alisa; Hu, Frank B et al. (2016) Whole Grain Intake and Mortality From All Causes, Cardiovascular Disease, and Cancer: A Meta-Analysis of Prospective Cohort Studies. Circulation 133:2370-80

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