Obesogenic effects of chlorpyrifos and its metabolites during the differentiation of 3T3-L1 preadipocytes

Self Cite

Developmental exposure to toxicants and diet can interact with an individual’s genetics and produce long-lasting metabolic adaptations. The different isoforms of the apolipoprotein E (APOE) are an important source of variability in metabolic disorders and influence the response to the pesticide chlorpyrifos (CPF). We aimed to study the epigenetic regulation on feeding control genes and the influence of postnatal CPF exposure, APOE genotype, and sex, and how these modifications impact on the metabolic response to a high-fat diet (HFD). Both male and female apoE3- and apoE4-TR mice were exposed to CPF on postnatal days 10–15. The DNA methylation pattern of proopiomelanocortin, neuropeptide Y, leptin receptor, and insulin-like growth factor 2 was studied in the hypothalamus. At adulthood, the mice were given a HFD for eight weeks. The results highlight the importance of sex in the epigenetic regulation and the implication of CPF treatment and APOE genotype. The body weight progression exhibited sex-dimorphic differences, apoE4-TR males being the most susceptible to the effects induced by CPF and HFD. Overall, these results underscore the pivotal role of sex, APOE genotype, and developmental exposure to CPF on subsequent metabolic disturbances later in life and show that sex is a key variable in epigenetic regulation.

Section: Introductionsupporting

confidence: 63%

Sex and Exposure to Postnatal Chlorpyrifos Influence the Epigenetics of Feeding-Related Genes in a Transgenic APOE Mouse Model: Long-Term Implications on Body Weight after a High-Fat Diet

Guardia-Escote

Blanco

Basaure

et al. 2020

Self Cite

“…Experiments were carried out using various models of adipocyte cell lines such as the cell line murine 3T3-L1, primary cultures of fat depots recovered from animal or human donors, and transfected cells coupled to gene reporter assays. Chemicals leading to lipid accumulation included organophosphorous pesticides [ 138 , 139 ], imidazole fungicide triflumizole [ 140 ], various flame retardants [ 141 , 142 , 143 , 144 ], parabens, and musk compounds [ 125 , 145 ], DDT/DDE [ 146 , 147 ]. As for bisphenols and phthalates, the activation of PPARγ has not been systematically reported suggesting the involvement of other mechanisms to induce lipid accumulation.…”

Section: Overview Of Metabolic Disruptors and Edcs Targeting The Amentioning

confidence: 99%

Adipose Tissue and Endocrine-Disrupting Chemicals: Does Sex Matter?

Magueresse-Battistoni

2020

Obesity and metabolic-related diseases, among which diabetes, are prominent public health challenges of the 21st century. It is now well acknowledged that pollutants are a part of the equation, especially endocrine-disrupting chemicals (EDCs) that interfere with the hormonal aspect. The aim of the review is to focus on adipose tissue, a central regulator of energy balance and metabolic homeostasis, and to highlight the significant differences in the endocrine and metabolic aspects of adipose tissue between males and females which likely underlie the differences of the response to exposure to EDCs between the sexes. Moreover, the study also presents an overview of several mechanisms of action by which pollutants could cause adipose tissue dysfunction. Indeed, a better understanding of the mechanism by which environmental chemicals target adipose tissue and cause metabolic disturbances, and how these mechanisms interact and sex specificities are essential for developing mitigating and sex-specific strategies against metabolic diseases of chemical origin. In particular, considering that a scenario without pollutant exposure is not a realistic option in our current societies, attenuating the deleterious effects of exposure to pollutants by acting on the gut-adipose tissue axis may constitute a new direction of research.

“…The organophosphorus insecticide chlorpyrifos seems to be one of the potential obesogenic worldwide [ 109 , 110 ]. However, the results of our analysis seem to be contradictory.…”

Section: Discussionmentioning

confidence: 99%

“…These mechanisms may lead to metabolic disruption, such as insulin resistance and changes in body weight, as observed in adult mice exposed to CPF [ 112 ]. In this regard, chlorpyrifos seems to have an influence over the leptin and insulin signaling pathway [ 113 ] and on the adipogenic process facilitating lipid storage [ 110 ]. Some studies have shown that the gut microbiota could play an essential role in these effects [ 114 , 115 ].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Prenatal or Postnatal Exposure to Pesticides and Obesity: A Systematic Review

Pinos

Carrillo

Merchán

et al. 2021

Self Cite

In recent years, the worldwide prevalence of overweight and obesity among adults and children has dramatically increased. The conventional model regarding the onset of obesity is based on an imbalance between energy intake and expenditure. However, other possible environmental factors involved, such as the exposure to chemicals like pesticides, cannot be discarded. These compounds could act as endocrine-disrupting chemicals (EDC) that may interfere with hormone activity related to several mechanisms involved in body weight control. The main objective of this study was to systematically review the data provided in the scientific literature for a possible association between prenatal and postnatal exposure to pesticides and obesity in offspring. A total of 25 human and 9 animal studies were analyzed. The prenatal, perinatal, and postnatal exposure to organophosphate, organochlorine, pyrethroid, neonicotinoid, and carbamate, as well as a combined pesticide exposure was reviewed. This systematic review reveals that the effects of pesticide exposure on body weight are mostly inconclusive, finding conflicting results in both humans and experimental animals. The outcomes reviewed are dependent on many factors, including dosage and route of administration, species, sex, and treatment duration. More research is needed to effectively evaluate the impact of the combined effects of different pesticides on human health.