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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.

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Induction of obesity in rats by ATZ treatment.(A and B) Changes in body weight of ATZ-treated rats (ATZ30, 30 µg kg−1 day−1; ATZ300, 300 µg kg−1 day−1) versus control rats over time. (A) Regular-diet group. Rats were fed a regular diet for 5 months during treatment with ATZ, provided in drinking water. (B) High-fat-diet group. Rats were fed a regular diet for 3 months and then fed a high-fat diet for another 2 months. (C) End-of-study comparison of body weights between two different diet-treated rats. (D and E) Increase in visceral fat by ATZ. The amount of visceral fat in the high-fat diet group was measured by horizontal CT scan. Abdominal fat area at the L3 level (D) and over L1 to L5 (E) were calculated from the scanned image using a Hounsfield unit. (E and F) Intracellular fat deposition by ATZ. The amount of intrahepatic (F) and intramuscular (G) fat in rats on a regular diet was measured by non-invasive 1H-MRS and adjusted for body weight. (*p<0.05, **p<0.01 vs. control).
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pone-0005186-g001: Induction of obesity in rats by ATZ treatment.(A and B) Changes in body weight of ATZ-treated rats (ATZ30, 30 µg kg−1 day−1; ATZ300, 300 µg kg−1 day−1) versus control rats over time. (A) Regular-diet group. Rats were fed a regular diet for 5 months during treatment with ATZ, provided in drinking water. (B) High-fat-diet group. Rats were fed a regular diet for 3 months and then fed a high-fat diet for another 2 months. (C) End-of-study comparison of body weights between two different diet-treated rats. (D and E) Increase in visceral fat by ATZ. The amount of visceral fat in the high-fat diet group was measured by horizontal CT scan. Abdominal fat area at the L3 level (D) and over L1 to L5 (E) were calculated from the scanned image using a Hounsfield unit. (E and F) Intracellular fat deposition by ATZ. The amount of intrahepatic (F) and intramuscular (G) fat in rats on a regular diet was measured by non-invasive 1H-MRS and adjusted for body weight. (*p<0.05, **p<0.01 vs. control).

Mentions: After being fed a normal diet for 3 months, control and the ATZ-treated rats exhibited no significant differences in mean body weight. From month 4 onward, mean body weight in the regular-diet groups was higher for ATZ-treated rats than for control rats. At the end of the study, the body weights of the regular-diet rats were 582.3±9.3 g for the 30-µg kg−1 day−1 ATZ group (ATZ30), 585.0±22.7 g for the 300-µg kg−1 day−1 ATZ group (ATZ300) and 554.6±13.4 g for controls; overall, the mean body weight of ATZ-treated rats was 5.5% higher than that of the controls (p<0.05; Fig. 1A and 1C). In the high-fat diet groups, the body weights of ATZ30 and ATZ300 groups were 621.1±18.8 g and 626.9±16.9 g, respectively, or 9.8% higher overall than control rats (570.8±13.6 g) (p<0.01, Fig. 1B and 1C). No treatment-related differences in food/water intake or horizontal/spontaneous locomotor activities were observed at any point. Thus, chronic exposure to low concentrations of ATZ resulted in weight gain, particularly when combined with a high-fat diet.


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)

Induction of obesity in rats by ATZ treatment.(A and B) Changes in body weight of ATZ-treated rats (ATZ30, 30 µg kg−1 day−1; ATZ300, 300 µg kg−1 day−1) versus control rats over time. (A) Regular-diet group. Rats were fed a regular diet for 5 months during treatment with ATZ, provided in drinking water. (B) High-fat-diet group. Rats were fed a regular diet for 3 months and then fed a high-fat diet for another 2 months. (C) End-of-study comparison of body weights between two different diet-treated rats. (D and E) Increase in visceral fat by ATZ. The amount of visceral fat in the high-fat diet group was measured by horizontal CT scan. Abdominal fat area at the L3 level (D) and over L1 to L5 (E) were calculated from the scanned image using a Hounsfield unit. (E and F) Intracellular fat deposition by ATZ. The amount of intrahepatic (F) and intramuscular (G) fat in rats on a regular diet was measured by non-invasive 1H-MRS and adjusted for body weight. (*p<0.05, **p<0.01 vs. control).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2664469&req=5

pone-0005186-g001: Induction of obesity in rats by ATZ treatment.(A and B) Changes in body weight of ATZ-treated rats (ATZ30, 30 µg kg−1 day−1; ATZ300, 300 µg kg−1 day−1) versus control rats over time. (A) Regular-diet group. Rats were fed a regular diet for 5 months during treatment with ATZ, provided in drinking water. (B) High-fat-diet group. Rats were fed a regular diet for 3 months and then fed a high-fat diet for another 2 months. (C) End-of-study comparison of body weights between two different diet-treated rats. (D and E) Increase in visceral fat by ATZ. The amount of visceral fat in the high-fat diet group was measured by horizontal CT scan. Abdominal fat area at the L3 level (D) and over L1 to L5 (E) were calculated from the scanned image using a Hounsfield unit. (E and F) Intracellular fat deposition by ATZ. The amount of intrahepatic (F) and intramuscular (G) fat in rats on a regular diet was measured by non-invasive 1H-MRS and adjusted for body weight. (*p<0.05, **p<0.01 vs. control).
Mentions: After being fed a normal diet for 3 months, control and the ATZ-treated rats exhibited no significant differences in mean body weight. From month 4 onward, mean body weight in the regular-diet groups was higher for ATZ-treated rats than for control rats. At the end of the study, the body weights of the regular-diet rats were 582.3±9.3 g for the 30-µg kg−1 day−1 ATZ group (ATZ30), 585.0±22.7 g for the 300-µg kg−1 day−1 ATZ group (ATZ300) and 554.6±13.4 g for controls; overall, the mean body weight of ATZ-treated rats was 5.5% higher than that of the controls (p<0.05; Fig. 1A and 1C). In the high-fat diet groups, the body weights of ATZ30 and ATZ300 groups were 621.1±18.8 g and 626.9±16.9 g, respectively, or 9.8% higher overall than control rats (570.8±13.6 g) (p<0.01, Fig. 1B and 1C). No treatment-related differences in food/water intake or horizontal/spontaneous locomotor activities were observed at any point. Thus, chronic exposure to low concentrations of ATZ resulted in weight gain, particularly when combined with a high-fat diet.

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