Authors
C. Pelletier et al., Toxicological Sciences (67):46-51, 2002.

Associations between weight loss-induced changes in plasma organochlorine concentrations, serum T3 concentration, and resting metabolic rate

During the past 60-70 years organochlorine compounds have been widely used as pesticides, insecticides, and multipurpose industrial chemicals. A large number of these compounds have been shown to produce mutagenic, immunotoxic, and carcinogenic effects (i.e. PCBs, dioxins). They also affect endocrine homeostasis by mimicking the action of endogenous hormones or altering their levels in the circulation. The production of some of these compounds has been terminated in many countries; however, most toxic dibenzofurans and dibenzodioxins continue to be produced as byproducts of chemical manufacturing processes and the combustion of fossil fuels and waste incineration.

Thyroid function impairment is among the many adverse effects of organochlorines reported in animals and humans. In particular, these compounds have been shown to decrease the level of plasma T4 by displacing this hormone from protein binding and increasing its hepatic metabolism by inducing the UDP-glucuronyltransferase enzyme. Since organochlorines are lipophilic compounds, they accumulate in adipose tissue. However, the concentration of organochlorine compounds increases in plasma, adipose tissue, and various other tissues (i.e. muscle, liver) following body weight loss. Thyroid hormones directly affect resting metabolic rate (RMR), appetite, and body weight. Body weight loss decreases energy expenditure which is due in part to changes in thyroid hormones, catecholamine release, and carbohydrate utilization. The authors of the present investigation sought to determine whether a weight loss induced increase in plasma organochlorine concentration might affect serum T3 concentration and RMR.

Pelletier et al. measured plasma concentrations of seventeen organochlorine compounds, serum T3 concentrations, and RMR of 16 obese men who followed a macronutrient-specific energy-restricted diet for 15 weeks. All measurements were performed before and after weight loss. Following weight loss, the concentrations of thirteen organochlorines were significantly increased, and this increase was correlated with a decrease in T3 concentration and RMR. Changes in T3 concentration were not significantly correlated with those in RMR after weight loss. However, a stepwise multiple regression analysis determined that changes in organochlorine concentrations during weight loss were the best predictor of changes in RMR (32% of variance). The mobilization of organochlorines from fat depots following weight loss is likely to produce high local tissue concentrations of these compounds. It has been suggested that the redistribution of these compounds in various tissues may be associated with the weight regain that often occurs after weight loss. One hypothesis states that increased organochlorine concentrations following weight loss might subsequently induce a positive energy balance by reducing the RMR and thus promoting body fat accumulation. Body fat accumulation might be a way of protecting against the harmful effects of organochlorines by storing these compounds and preventing their contact with target organs. However, toxic effects of organochlorine concentrations released from adipose tissue following weight loss have not yet been assessed.

This study is limited to its small sample size and the possibility that confounding factors, such as altered fat mass, fat-free mass, and leptin concentrations promoted by weight loss, were responsible for the decreased plasma T3 concentration and RMR. Nevertheless, the results of this study suggest that weight loss-promoted changes in organochlorine compound concentrations were associated with decreased plasma T3 concentration and RMR. Moreover, the results of this study have implications for potential adverse health effects in individuals with illness induced weight loss and in the elderly.