Limits...
Chronic exposure to the herbicide, atrazine, causes mitochondrial dysfunction and insulin resistance.

Lim S, Ahn SY, Song IC, Chung MH, Jang HC, Park KS, Lee KU, Pak YK, Lee HK - PLoS ONE (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

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 microg 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.

Show MeSH

Related in: MedlinePlus

Mitochondrial OXPHOS activity of ATZ-treated rat skeletal muscle mitochondria.Rats on a regular diet were treated with or without ATZ for 5 months. (A) Dose-dependent decrease in energy expenditure in ATZ-treated rats, monitored using indirect calorimetry. (B) Decrease in OCR of complex II plus III in ATZ300-treated skeletal muscle mitochondria (n = 5). (C) Decrease in the activity of complex III enzyme in ATZ-treated liver lysates, determined by spectrophotometry (*p<0.05, **p<0.01; n = 5). (D) Western blot of muscle mitochondria proteins. Total skeletal muscle mitochondrial lysates from rats on a regular diet were subjected to western blot analysis using the indicated antibodies.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2664469&req=5

pone-0005186-g004: Mitochondrial OXPHOS activity of ATZ-treated rat skeletal muscle mitochondria.Rats on a regular diet were treated with or without ATZ for 5 months. (A) Dose-dependent decrease in energy expenditure in ATZ-treated rats, monitored using indirect calorimetry. (B) Decrease in OCR of complex II plus III in ATZ300-treated skeletal muscle mitochondria (n = 5). (C) Decrease in the activity of complex III enzyme in ATZ-treated liver lysates, determined by spectrophotometry (*p<0.05, **p<0.01; n = 5). (D) Western blot of muscle mitochondria proteins. Total skeletal muscle mitochondrial lysates from rats on a regular diet were subjected to western blot analysis using the indicated antibodies.

Mentions: Insulin resistance and obesity are affected by caloric intake, physical activity and energy expenditure [31], [32]. Since no treatment-related changes in food or water intake or physical activity were observed at any point during the study, the development of insulin resistance by ATZ might be related to energy metabolism. To determine if ATZ affected energy metabolism, we measured energy expenditure and OCR using indirect calorimetry and oxygen sensors, respectively. The energy expenditure of ATZ-treated rats on regular diet was reduced in a dose-dependent manner (Fig. 4A). The OCR of each OXPHOS complex was measured using mitochondria isolated from the soleus muscle of ATZ-treated rats on regular diet. The combined OCR measured for complexes II plus III, both of which use ubiquinone (Q) as an electron transfer intermediate, was significantly reduced by ATZ administration. The activities of other complexes were not altered (Fig. 4B), although the OCR of complex I showed a tendency toward a decrease that did not reach statistical significance. There were some analytical limitations in measuring OCR where the changes were modest, especially when using animal tissues.


Chronic exposure to the herbicide, atrazine, causes mitochondrial dysfunction and insulin resistance.

Lim S, Ahn SY, Song IC, Chung MH, Jang HC, Park KS, Lee KU, Pak YK, Lee HK - PLoS ONE (2009)

Mitochondrial OXPHOS activity of ATZ-treated rat skeletal muscle mitochondria.Rats on a regular diet were treated with or without ATZ for 5 months. (A) Dose-dependent decrease in energy expenditure in ATZ-treated rats, monitored using indirect calorimetry. (B) Decrease in OCR of complex II plus III in ATZ300-treated skeletal muscle mitochondria (n = 5). (C) Decrease in the activity of complex III enzyme in ATZ-treated liver lysates, determined by spectrophotometry (*p<0.05, **p<0.01; n = 5). (D) Western blot of muscle mitochondria proteins. Total skeletal muscle mitochondrial lysates from rats on a regular diet were subjected to western blot analysis using the indicated antibodies.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2664469&req=5

pone-0005186-g004: Mitochondrial OXPHOS activity of ATZ-treated rat skeletal muscle mitochondria.Rats on a regular diet were treated with or without ATZ for 5 months. (A) Dose-dependent decrease in energy expenditure in ATZ-treated rats, monitored using indirect calorimetry. (B) Decrease in OCR of complex II plus III in ATZ300-treated skeletal muscle mitochondria (n = 5). (C) Decrease in the activity of complex III enzyme in ATZ-treated liver lysates, determined by spectrophotometry (*p<0.05, **p<0.01; n = 5). (D) Western blot of muscle mitochondria proteins. Total skeletal muscle mitochondrial lysates from rats on a regular diet were subjected to western blot analysis using the indicated antibodies.
Mentions: Insulin resistance and obesity are affected by caloric intake, physical activity and energy expenditure [31], [32]. Since no treatment-related changes in food or water intake or physical activity were observed at any point during the study, the development of insulin resistance by ATZ might be related to energy metabolism. To determine if ATZ affected energy metabolism, we measured energy expenditure and OCR using indirect calorimetry and oxygen sensors, respectively. The energy expenditure of ATZ-treated rats on regular diet was reduced in a dose-dependent manner (Fig. 4A). The OCR of each OXPHOS complex was measured using mitochondria isolated from the soleus muscle of ATZ-treated rats on regular diet. The combined OCR measured for complexes II plus III, both of which use ubiquinone (Q) as an electron transfer intermediate, was significantly reduced by ATZ administration. The activities of other complexes were not altered (Fig. 4B), although the OCR of complex I showed a tendency toward a decrease that did not reach statistical significance. There were some analytical limitations in measuring OCR where the changes were modest, especially when using animal tissues.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

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 microg 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.

Show MeSH
Related in: MedlinePlus