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 #
5R01ES022981-04
Application #
9265461
Study Section
Kidney, Nutrition, Obesity and Diabetes Study Section (KNOD)
Program Officer
Schug, Thaddeus
Project Start
2014-07-01
Project End
2019-04-30
Budget Start
2017-05-01
Budget End
2019-04-30
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Harvard University
Department
Nutrition
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Zong, Geng; Valvi, Damaskini; Coull, Brent et al. (2018) Persistent organic pollutants and risk of type 2 diabetes: A prospective investigation among middle-aged women in Nurses' Health Study II. Environ Int 114:334-342
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
Chiu, Yu-Han; Williams, Paige L; Mínguez-Alarcón, Lidia et al. (2018) Comparison of questionnaire-based estimation of pesticide residue intake from fruits and vegetables with urinary concentrations of pesticide biomarkers. J Expo Sci Environ Epidemiol 28:31-39
Zong, Geng; Lebwohl, Benjamin; Hu, Frank B et al. (2018) Gluten intake and risk of type 2 diabetes in three large prospective cohort studies of US men and women. Diabetologia 61:2164-2173
Hu, Yang; Zong, Geng; Liu, Gang et al. (2018) Smoking Cessation, Weight Change, Type 2 Diabetes, and Mortality. N Engl J Med 379:623-632
Liu, G; Liang, L; Bray, G A et al. (2017) Thyroid hormones and changes in body weight and metabolic parameters in response to weight loss diets: the POUNDS LOST trial. Int J Obes (Lond) 41:878-886
Liu, Gang; Zong, Geng; Hu, Frank B et al. (2017) Cooking Methods for Red Meats and Risk of Type 2 Diabetes: A Prospective Study of U.S. Women. Diabetes Care 40:1041-1049
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
Liu, Gang; Zong, Geng; Doty, Richard L et al. (2016) Prevalence and risk factors of taste and smell impairment in a nationwide representative sample of the US population: a cross-sectional study. BMJ Open 6:e013246

Showing the most recent 10 out of 15 publications