Alterations of Systemic and Hepatic Metabolic Function Following Exposure to Trans-nonachlor in Low and High Fat Diet Fed Male Sprague Dawley Rats

The overall prevalence of metabolic diseases such as type 2 diabetes (T2D) and associated co-morbidities have increased at an alarming rate in the United States and worldwide. There is a growing body of epidemiological evidence implicating exposure to persistent organic pollutants (POPs), including legacy organochlorine (OC) pesticides and their bioaccumulative metabolites, in the pathogenesis of metabolic diseases. Therefore, the goal of the present study was to determine if exposure to trans-nonachlor, a bioaccumulative OC pesticide contaminant, in concert with high fat diet intake induced metabolic dysfunction. Briefly, male Sprague Dawley rats were exposed to trans-nonachlor (.5 or 5 ppm) in either a low fat (LFD) or high fat diet (HFD) for 16 weeks. At 8 weeks of intake, trans-nonachlor decreased serum triglyceride levels in LFD and HFD fed animals and at 16 weeks compared to LFD fed animals. Interestingly, serum glucose levels were decreased by trans-nonachlor (5 ppm) in LFD fed animals at 16 weeks. Serum free fatty acids were increased by trans-nonachlor exposure (5 ppm) in LFD fed animals at 16 weeks. HFD fed animals displayed signs of hepatic steatosis including elevated liver triglycerides, liver enzymes, and liver lipid peroxidation which were not significantly altered by trans-nonachlor exposure. However, there was a trans-nonachlor mediated increase in expression of fatty acid synthase in livers of LFD fed animals and not HFD fed animals. Thus, the present data indicate exposure to trans-nonachlor in conjunction with LFD or HFD intake produces both diet and exposure dependent effects on lipid and glucose metabolism.