Chronic exposure to the herbicide, atrazine, causes mitochondrial dysfunction and insulin resistance.
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.
Lim
Soo
S
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Ahn
Sun Young
SY
Song
In Chan
IC
Chung
Myung Hee
MH
Jang
Hak Chul
HC
Park
Kyong Soo
KS
Lee
Ki-Up
KU
Pak
Youngmi Kim
YK
Lee
Hong Kyu
HK
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001280:Atrazine / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D019069:Cell Respiration / Q000502:physiology; D004032:Diet; D005951:Glucose Tolerance Test; D006540:Herbicides / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D001786:Blood Glucose; D006540:Herbicides; D007328:Insulin; D008055:Lipids; D051057:Proto-Oncogene Proteins c-akt; D001280:Atrazine