Effects of high fat diet and perinatal dioxin exposure on development of body size and expression of platelet-derived growth factor receptor β in the rat brain

Abstract

Environmental exposure to dioxins, consumption of a high fat diet, and platelet-derived growth factor receptor β signaling in the brain affect feeding behavior, which is an important determinant of body growth. In the present study, we investigated the effects of prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and high fact diet after weaning on body growth and expression of platelet-derived growth factor receptor β in the brain in rat pups. Subjects from the control and dioxin exposure groups were assigned to 1 of 3 different diet groups: standard diet, high fat diet in the juvenile period, or high fat diet in adulthood. Body weight gain rate in the juvenile high fat diet group and the length gain rate in the adult high fat diet group were greater than the corresponding values in the standard diet group only in male offspring, although the effects of dioxin exposure on growth were not significant. Consumption of a high fat diet decreased platelet-derived growth factor receptor β levels in the amygdala and hippocampus in both sexes compared to control groups, while 2,3,7,8-tetrachlorodibenzo-p-dioxin decreased platelet-derived growth factor receptor platelet-derived growth factor receptor β levels in the amygdala and striatum only in females receiving an high fat diet. Furthermore, platelet-derived growth factor receptor β levels in the hippocampus and platelet-derived growth factor receptor β striatum were inversely correlated with increases in body length, while changes in platelet-derived growth factor receptor β in the amygdala and nucleus accumbens were significantly correlated to body weight gain or body mass index. In conclusion, these findings suggest that these 2,3,7,8-tetrachlorodibenzo-p-dioxin and high fat diet-induced changes in body growth and feeding behaviors might be partially mediated by changes in brain platelet-derived growth factor receptor β levels.

Elevated PDGF‐BB from Bone Impairs Hippocampal Vasculature by Inducing PDGFRβ Shedding from Pericytes

“…[ 20 ] Similar to age‐associated cerebrovascular phenotype, HFD also causes cerebrovascular impairment [ 22 ] and PDGF‐BB/PDGFR β signaling alteration in the brain. [ 23 ] We therefore assessed cerebrovascular changes in mice fed HFD. Consistently with our previous finding, elevated concentration of PDGF‐BB was also detected in both serum and plasma of mice fed HFD relative to the mice fed normal CHD, with 4.9‐fold and tenfold increase in serum and plasma, respectively (Figure S3A,S3B , Supporting Information).…”

Mu-opioid receptor and receptor tyrosine kinase crosstalk: Implications in mechanisms of opioid tolerance, reduced analgesia to neuropathic pain, dependence, and reward

“…Further studies to establish if this could be generalized to other opioids remain necessary. For example, PDGFRβ is also expressed in brain regions involved in reward and addiction such as mPFC, NAc and dStr ( Balayssac et al, 2009 ; Bor et al, 2017 ) and PDGFRβ levels were shown to be altered in the striatum and midbrain of rodents with disrupted dopaminergic signaling, a central component for reward signaling ( Masuo et al, 2004 ). Overall, this work suggests RTKs could be promising, yet understudied, candidates to mitigate morphine reward, especially IRs.…”

Sex-specific effects of perinatal dioxin exposure on eating behavior in 3-year-old Vietnamese children

“…Animal studies have reported that dioxin exposure affected brain regions in the limbic system such as the hypothalamus, nucleus accumbens, amygdala, and orbitofrontal cortex [ 13 – 16 ] that are involved in controlling appetite and food rewards [ 17 , 18 ], and altered taste preference in female rats exposed to dioxin perinatally [ 19 ]. Based on these findings, we hypothesized that dioxin may alter eating behaviors in children perinatally exposed to dioxin by affecting these brain regions.…”