Effects of developmental deltamethrin exposure on white adipose tissue gene expression

Abstract

Deltamethrin, a type II pyrethroid, is a widely used insecticide. The purpose of this study was to determine whether perinatal deltamethrin exposure altered the expression of adipogenic and lipogenic genes in white adipose tissue (WAT) in adult pups. C57BL/6 pregnant mice were administered 0, 1, or 3 mg/kg of deltamethrin orally every 3 days throughout gestation and lactation. Offspring were weaned on postnatal day 25, and WAT was collected from 5-month-old male mice. Perinatal deltamethrin exposure decreased the mRNA expression of adipogenesis-related transcription factors Pparγ, Cebpα, and lipogenic genes Srebp1c, Acc-1, Cd36, Lpl, Scd-1; along with Nrf2 and target genes Nqo1 and Gclc at the 1 mg/kg treatment. Cytokine expression of Fas/Tnf-R and Cd209e at the 1 mg/kg treatment was significantly decreased, and expression of Tnf, Cd11c, and Fas/Tnf-R was decreased at the 3 mg/kg treatment. Developmental deltamethrin exposure did not overtly affect body weight or adipose weight, but decreased mRNA expression of specific genes that may potentially disrupt normal adipogenesis and lipid and glucose metabolism if the offspring are challenged by changes in diet or environment.

FIGURE 1

Body weight was used to describe any potential metabolic effects of perinatal deltamethrin exposure, along with blood glucose concentration and mRNA gene expression of key factors in insulin response of WAT to describe potential effects on glucose homeostasis. Body weights of 5-month-old male mice were taken prior to sacrifice. (A) Average body weight (g) of each treatment group expressed as a mean BW ± SEM (n =6–7). (B) Blood glucose level taken at time of necropsy of 5-month-old adult male mice expressed as a mean BG ± SEM (n = 5–6–). mRNA gene expression data in WAT of 5-month-old adult male mouse pups from dams exposed to 0,1, or3 mg deltamethrin/kg every 3 days during getation and lactation. Total RNA was isolated from WAT, and mRNA levels were Quantified by Quantigene Plex 2.0 assay. All gene expression data were normalized to Rpl13a (no significant change in gene expression) and are expressed as mean ± SEM (n = 8–9). (C) Insulin responsive and glucose transport: Irs-1, Glut-4, Glut- 2 mRNA expression. mRNA gene expression data in WAT of 5-month-old adult male mouse pups from dams exposed to 0, 1, or 3 mg deltamethrin/kg every 3 days during gestation and lactation. * and # represent statistical difference between control and treatment doses (p < 0.05 and p < 0.005, respectively).

FIGURE 2

mRNA gene expression data in WAT of 5-month-old adult male mouse pups from dams exposed to 0, 1, or 3 mg deltamethrin/kg every 3 days during gestation and lactation. Total RNA was isolated from WAT, and mRNA levels were quantified by Quantigene Plex 2.0 assay. All gene expression data were normalized to Rpl13a (no significant change in gene expression) and are expressed as mean ± SEM (n = 8–9). (A) Lipogenic genes: Srebp1, Acc-1, Fabp4, Cd36, Lpl, Scd-1 mRNA expression. (B) Regulators of adipogenesis: Pparγ , Cebpα, Cebpβ mRNA expression. (C) mRNA gene expression for Nrf2, Nqo1, and Gclc was quantified by a Light-cycler 480 SYBR green qPCR method. Nrf2, Nqo1, and Gclc mRNA expression * and # represent statistical difference between control and treatment doses (p < 0.05 and p < 0.005, respectively).

FIGURE 3

mRNA gene expression of cytokines in WAT of 5-month-old adult male pups from dams exposed to 0, 1, or 3 mg deltamethrin/kg every 3 days during gestation and lactation. Total RNA was isolated from WAT, and mRNA levels were quantified by Quantigene Plex 2.0 assay. All gene expression data were normalized to Rpl13a (no significant change in gene expression) and are expressed as mean ± SEM (n = 8–9) Cytokines: Tnf, Ccl-2, Cd11c, Fas/Tnf-R (M1 macrophage markers) and Cd209e (M2 macrophage marker). * and # represent statistical difference between control and treatment doses (p < 0.05 and p < 0.005, respectively).