Chronic Exposure to the Herbicide, Atrazine, Causes Mitochondrial Dysfunction and Insulin Resistance

Abstract

There is an apparent overlap between areas in the USA where the herbicide, atrazine (ATZ), is heavily used and obesity-prevalence maps of people with a BMI over 30. Given that herbicides act on photosystem II of the thylakoid membrane of chloroplasts, which have a functional structure similar to mitochondria, we investigated whether chronic exposure to low concentrations of ATZ might cause obesity or insulin resistance by damaging mitochondrial function. Sprague-Dawley rats (n = 48) were treated for 5 months with low concentrations (30 or 300 µg kg−1 day−1) of ATZ provided in drinking water. One group of animals was fed a regular diet for the entire period, and another group of animals was fed a high-fat diet (40% fat) for 2 months after 3 months of regular diet. Various parameters of insulin resistance were measured. Morphology and functional activities of mitochondria were evaluated in tissues of ATZ-exposed animals and in isolated mitochondria. Chronic administration of ATZ decreased basal metabolic rate, and increased body weight, intra-abdominal fat and insulin resistance without changing food intake or physical activity level. A high-fat diet further exacerbated insulin resistance and obesity. Mitochondria in skeletal muscle and liver of ATZ-treated rats were swollen with disrupted cristae. ATZ blocked the activities of oxidative phosphorylation complexes I and III, resulting in decreased oxygen consumption. It also suppressed the insulin-mediated phosphorylation of Akt. These results suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a high-fat diet is prevalent.

Genetic and environmental factors associated with type 2 diabetes and diabetic vascular complications

“…These findings have biologic plausibility exemplified in several experimental models. Exposure to the herbicide atrazine (ATZ) can cause mitochondrial toxicity and promote obesity and insulin resistance, with even more detrimental effects observed when animals were fed a high-fat diet [58]. Pesticides can suppress the expression of functional glucose transporter proteins in several organs, providing a hypothetical mechanism for the observed link between these chemicals and insulin resistance [59].…”

Effects of Herbicide Atrazine in Experimental Animal Models

“…Study performed in SpragueDawley rats treated for 5 months with vehicle or ATZ (30 or 300 µg kg -1 day -1 ), supplied in drinking water, showed prominent accumulation of lipid droplets in the livers of ATZtreated rats (Lim et al, 2009). By means of transmission electron microscopy, some liver mitochondria from the ATZ-treated group showed partially disrupted cristae.…”

“…Despite the fact that mitochondrial morphology was altered in liver and, additionally, in muscle, protein expression levels of mitochondrial OXPHOS complex subunits in liver and muscle tissues were not changed significantly by ATZ administration. Since no treatment-related changes in food or water intake or physical activity were observed at any point during the study, Lim et al (2009) believe that the development of insulin resistance by ATZ might be related to energy metabolism and they suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a highfat diet is prevalent.…”

Are Environmental Contaminants Responsible for ‘Globesity’?

“…Recent studies have also proven that chronic exposure to the herbicide Atrazine or mixed persistent organic pollutants were responsible for visceral obesity, insulin resistance, and dyslipidemia [118][119].…”