Developmental exposure to the endocrine disruptor tolylfluanid induces sex-specific later-life metabolic dysfunction

Ruíz, Daniel; Regnier, S.; Kirkley, Andrew G.; Hara, Manami; Haro, Fidel; Aldirawi, Hani; Dybala, Michael P.; Sargis, Robert M.

doi:10.1016/j.reprotox.2019.06.010

Cited by 14 publications

(6 citation statements)

References 45 publications

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“…Developmental exposure to TF, at a dose of 67 mg/kg/day via the diet, similar to the dose used in the adult study [141], resulted in lower birth weight, reduced weaning weight and reduced adiposity in adult female offspring with no change in males [600]. It is likely that the dose given during pregnancy, while the same as given to adults, was too high and thus was toxic to the developing fetus.…”

Section: Tolylfluanidmentioning

confidence: 91%

Obesity II: Establishing causal links between chemical exposures and obesity

Heindel¹,

Howard²,

Agay-Shay³

et al. 2022

Biochemical Pharmacology

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103

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Section: Tolylfluanidmentioning

confidence: 91%

Obesity II: Establishing causal links between chemical exposures and obesity

Heindel¹,

Howard²,

Agay-Shay³

et al. 2022

Biochemical Pharmacology

Self Cite

103

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“…The adipose tissues and the liver are major metabolic tissues targeted by GCs (Lee et al, 2018, Vegiopoulos andHerzig, 2007). Interestingly early life exposure to tolylfluanid (TF) a GR agonist was found to induce sex-specific later-life metabolic dysfunction (Ruiz et al, 2019). Female mice showed enhanced systemic insulin sensitivity, reduced adiposity and normal hepatic gluconeogenic activities while males had impaired glucose tolerance and no changes of adiposity.…”

Section: Metabolic Disruptors That Alter Gr Signaling Pathways In a Sex-dimorphic Patternmentioning

confidence: 99%

Endocrine disrupting chemicals and metabolic disorders in the liver: What if we also looked at the female side?

Magueresse-Battistoni

2021

Chemosphere

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Endocrine disrupting chemicals (EDCs) are linked to the worldwide epidemic incidence of metabolic disorders and fatty liver diseases, which affects quality of life and represents a high economic cost to society. Energy homeostasis exhibits strong sexual dimorphic traits, and metabolic organs respond to EDCs depending on sex, such as the liver, which orchestrates both drug elimination and glucose and lipid metabolism. In addition, fatty liver diseases show a strong sexual bias, which in part could also originate from sex differences observed in gut microbiota. The aim of this review is to highlight significant differences in endocrine and metabolic aspects of the liver, between males and females throughout development and into adulthood. It is also to illustrate how the male and female liver differently cope with exposure to various EDCs such as bisphenols, phthalates and persistent organic chemicals in order to draw attention to the need to include both sexes in experimental studies.Interesting data come from analyses of the composition and diversity of the gut microbiota in males exposed to the mentioned EDCs showing significant correlations with hepatic lipid accumulation and metabolic disorders but information on females is lacking or incomplete. As industrialization increases, the list of anthropogenic chemicals to which humans will be exposed will also likely increase. In addition to strengthening existing regulations, encouraging populations to protect themselves and promoting the substitution of harmful chemicals with safe products, innovative strategies based on sex differences in the gut microbiota and in the gut-liver axis could be optimistic outlook.

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“…In vitro experiments using the 3T3-L1 cell culture model demonstrated that TF had GR-agonist activities [ 130 ]. Moreover, perinatal exposure to TF showed sex-specific adverse effects on the adipose tissue [ 192 ] which may have epigenetic basis [ 193 ] at least in males (females had not been studied). Indeed, adult males had impaired glucose tolerance but no changes of adiposity if exposed perinatally while they showed enhanced body weight, adiposity, and insulin resistance if exposed during adulthood [ 194 ].…”

Section: Edcs Mimicking Sex Steroid or Altering Active Sex Steroidmentioning

confidence: 99%

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

Magueresse-Battistoni

2020

IJERPH

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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.

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Developmental exposure to the endocrine disruptor tolylfluanid induces sex-specific later-life metabolic dysfunction

Cited by 14 publications

References 45 publications

Obesity II: Establishing causal links between chemical exposures and obesity

Obesity II: Establishing causal links between chemical exposures and obesity

Endocrine disrupting chemicals and metabolic disorders in the liver: What if we also looked at the female side?

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

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