Permethrin alters glucose metabolism in conjunction with high fat diet by potentiating insulin resistance and decreases voluntary activities in female C57BL/6J mice

Abstract

Permethrin, a type 1 pyrethroid insecticide, was previously reported to promote adipogenesis in 3T3-L1 adipocytes and insulin resistance in C2C12 muscle cells; however, the effects of permethrin exposure on glucose and lipid metabolisms in vivo remain unknown. The purpose of this study was to investigate the effects of permethrin exposure on glucose and lipid homeostasis as well as voluntary movement in female mice in response to dietary fat. We tested three doses of permethrin (50, 500, & 5000 μg/kg body weight/day) in low fat diet-fed (4% w/w of diet) and high fat diet-fed (20% w/w of diet) female C57BL/6J mice for twelve weeks. Our results demonstrated that permethrin treatment potentiated high fat diet-induced insulin resistance as indicated by insulin tolerance tests, glucose tolerance tests, and homeostasis model assessment - insulin resistance (HOMA-IR) without altering weight or fat mass. Permethrin treatment significantly decreased voluntary movement and elevated blood glucose and insulin levels. Western blot results further showed that permethrin impaired insulin signaling via the Akt signaling pathway in the gastrocnemius muscle. Taken together, these results suggest that oral administration of permethrin potentiated high fat diet-induced insulin resistance, possibly increasing the risk of type 2 diabetes without altering weight gain in female C57BL/6J mice.

Exposure to permethrin promotes high fat diet-induced weight gain and insulin resistance in male C57BL/6J mice

“…To our knowledge, this is the first study reporting the potential role of permethrin in dietary fat-induced weight gain and insulin resistance in male mice. The current results along with previous report (Xiao, Kim, et al, 2017) suggest that there was a sex-dependent effect of permethrin on high fat diet-induced weight gain and insulin resistance. Increase intracellular calcium and ER stress may be contributed to altered adipogenesis and insulin resistance by permethrin (Basseri, et al, 2009; Cnop, et al, 2012; Draznin, et al, 1988; Jones, et al, 1996; Ozcan, et al, 2004; Sha, et al, 2009; Xiao, Qi, et al, 2017; Zemel, et al, 1995; Zemel, et al, 2000), although this does not explain the sex-dependent and tissue specific effects of permtherin.…”

“…The current and our previous report suggest sex-dependent responses to permethrin on high fat-diet induced weight gain (Xiao, Kim, et al, 2017). In the previous study, treatment with permethrin had no effect on weight gain in females, even though permethrin decreased voluntary activities, thus reducing energy expenditure, without any influence on energy intake (Xiao, Kim, et al, 2017). Since we did not measure voluntary activities in the current study, we are unable to make any conclusion whether permethrin influenced energy expenditure by altering activity levels in male mice.…”

“…The current study showed that daily administration of permethrin, at the NOAEL or lower doses, potentiated high fat diet-induced weight and fat mass gains as well as altered insulin resistance in male mice. Previously, permethrin was found to promote high fat diet-induced insulin resistance without effect on body weight in female mice (Xiao, Kim, et al, 2017). To our knowledge, this is the first study reporting the potential role of permethrin in dietary fat-induced weight gain and insulin resistance in male mice.…”

“…Kim, et al, 2013, 2014; Moreno-Aliaga, et al, 2002; Park, et al, 2013; Shen, et al, 2017; Sun, Peng, et al, 2017; Sun, Qi, et al, 2016; Xiao, Qi, et al, 2017; Xiao, Clark, et al 2017). In addition, permethrin treatment promoted high fat diet-induced insulin resistance in female mice (Xiao, Kim, et al, 2017); however, the effects of permethrin on high fat diet-induced obesity and insulin resistance in male mice remain unknown. Previously, several reports of sex-dependent effects of insecticides, particularly organochlorine, organophosphorus, and neonicotinoid insecticides, on weight gain have been reported (Lassiter & Brimijoin, 2008; Lassiter, Ryde, et al, 2008; Sun, Qi, et al, 2017; Sun, Xiao, et al, 2016; Villeneuve, et al, 1977; Xiao, Kim, et al 2017).…”

Longitudinal Study of Metabolic Biomarkers among Conventional and Organic Farmers in Thailand

“…Exposure to chlorpyrifos [34] and imidacloprid [35,36] increased the epididymal fat weight in mice fed a high-fat diet. Exposure to permethrin [37], diazinon [38], deltamethrin [39], chlorantraniliprole [40], and fipronil [41] were found to induce lipid accumulation by regulating the AMP-activated protein kinase (AMPK) pathway in mice. Male zebrafish exposed to the fungicide tebuconazole for 7 days showed increases in glucose, cholesterol, triglycerides, and lactate levels over those in the control fish [42].…”