Environmental Pollutants and Metabolic Disorders: The Multi-Exposure Scenario of Life

Obesity and diabetes have reached epidemic proportions the past few decades and continue to progress worldwide with no clear sign of decline of the epidemic. Obesity is of high concern because it is the main risk factor for a number of non-communicable diseases such as cardiovascular diseases and type 2 diabetes. Metabolic diseases constitute a major challenge as they are associated with an overall reduced quality of life and impose a heavy economic burden on countries. These are multifactorial diseases and it is now recognized that environmental exposure to man-made chemical pollutants is part of the equation. Yet, risk assessment procedures are based on a one-by-one chemical evaluation which does not meet the specificities of the multi-exposure scenario of life, e.g., a combined and long-term exposure to even the smallest amounts of chemicals. Indeed, it is assumed that environmental exposure to chemicals will be negligible based on the low potency of each chemical and that they do not interact. Within this mini-review, strong evidences are brought that exposure to low levels of multiple chemicals especially those shown to interfere with hormonal action, the so-called endocrine disrupting compounds do trigger metabolic disturbances in conditions in which no effect was expected if considering the concentration of each individual chemical in the mixture. This is known as the cocktail effect. It means that risk assessment procedures are not protective enough and thus that it should be revisited for the sake of Public Health

Chronic Consumption of Farmed Salmon Containing Persistent Organic Pollutants Causes Insulin Resistance and Obesity in Mice

Background: Dietary interventions are critical in the prevention of metabolic diseases. Yet, the effects of fatty fish consumption on type 2 diabetes remain unclear. The aim of this study was to investigate whether a diet containing farmed salmon prevents or contributes to insulin resistance in mice. Methodology/Principal Findings: Adult male C57BL/6J mice were fed control diet (C), a very high-fat diet without or with farmed Atlantic salmon fillet (VHF and VHF/S, respectively), and Western diet without or with farmed Atlantic salmon fillet (WD and WD/S, respectively). Other mice were fed VHF containing farmed salmon fillet with reduced concentrations of persistent organic pollutants (VHF/S-POPs). We assessed body weight gain, fat mass, insulin sensitivity, glucose tolerance, ex vivo muscle glucose uptake, performed histology and immunohistochemistry analysis, and investigated gene and protein expression. In comparison with animals fed VHF and WD, consumption of both VHF/S and WD/S exaggerated insulin resistance, visceral obesity, and glucose intolerance. In addition, the ability of insulin to stimulate Akt phosphorylation and muscle glucose uptake was impaired in mice fed farmed salmon. Relative to VHF/S-fed mice, animals fed VHF/S-POPs had less body burdens of POPs, accumulated less visceral fat, and had reduced mRNA levels of TNFa as well as macrophage infiltration in adipose tissue. VHF/S-POPs-fed mice further exhibited better insulin sensitivity and glucose tolerance than mice fed VHF/S. Conclusions/Significance: Our data indicate that intake of farmed salmon fillet contributes to several metabolic disorders linked to type 2 diabetes and obesity, and suggest a role of POPs in these deleterious effects. Overall, these findings may participate to improve nutritional strategies for the prevention and therapy of insulin resistance

L'exposition fœtale aux polluants alimentaires

Scientifiques et pouvoirs publics s’inquiètent du rôle éventuel que pourraient jouer les perturbateurs endocriniens dans l’apparition de certaines maladies chroniques, comme l’obésité et le diabète de type 2. Cette étude de faisabilité "DevPolEndo" visait justement à mettre au point un protocole pour déterminer si un mélange de polluants administré à faible dose, pouvait affecter la reproduction et le métabolisme de la descendance, et si l’obésité et l’âge de la mère constituaient des facteurs aggravants

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

International audienceEndocrine 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

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

International audienceObesity 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

MIGRATIONS CELLULAIRES ET RESTRUCTURATIONS TISSULAIRES DANS LA GONADE MALE (IMPLICATION DES METALLOPROTEASES)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Implication des sérine-protéases et des serpin dans la physiologie du testicule (incidence d'une exposition in utero aux dioxines sur la différenciation gonadique)

Le testicule est un tissu dynamique qui se caractérise par de multiples épisodes de migrations cellulaires et de restructurations tissulaires tout au long du développement et de la vie adulte. Ce projet s'est orienté sur le rôle des sérine-protéases et leurs inhibiteurs, les SERPIN, dans la physiologie testiculaire. Nous montrons que la SERPINA5 est exprimée à partir de 12,5 jpc dans les gonades mâles. Elle est localisée dans les cellules de Leydig et l'urokinase est une de ses protéases cibles. La SERPINA5 est aussi localisée dans les cellules germinales du testicule post-natal et adulte. Par ailleurs, nous démontrons que l'hormone trophique LH modifie l'activité protéolytique leydigienne, ce qui pourrait, en modulant l'espace extracellulaire, influer sur l'activité stéroïdogène de la cellule de Leydig. Nous avons également participé à une étude sur l'impact d'une exposition in utero aux dioxines sur l'acquisition de la fonction de reproduction chez le rat mâleLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Organogenèse testiculaire chez la souris, implications des protéases et des antiprotéases (conséquences de l'expositions in utéro à des perturbateurs endocriniens)

Ce travail de thèse d'université a été réalisé sur la souris et s'est orienté autour de 2 points: (i), l'étude du profil d'expression des protéases et de leurs inhibiteurs au cours de l'organogenèse testiculaire. Nous montrons que 2 inhibiteurs de protéases (TIMP-1 et PCI) présentent un dimorphisme d'expression mâle/femelle dans les phases précoces de la différenciation gonadique. TIMP-1 ne semble pas agir comme un inhibiteur des gélatinases; (ii), l'étude chez la souris, de l'incidence d'une exposition in utero au Bisphenol A (BPA) et au Diéthylstilbestrol (DES), sur l'organogenèse testiculaire. Dans nos conditions expérimentales, nous ne montrons aucun effet du BPA sur la différenciation testiculaire et sur la capacité de prolifération des cellules germinales. En ce qui concerne le DES, nous montrons que la baisse de testostérone par les testicules de foetus exposés in utero résulte d'une chute de l'expression de StAR et de la P450c17. Cet effet n'est pas dû à une atteinte de SF-1.LYON1-BU.Sciences (692662101) / SudocSudocFranceF

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

International audienceObesity and metabolic-related diseases among which diabetes are prominent public health challenges of the 21 st century. It is now well acknowledged that pollutants are part of the equation, especially endocrine disrupting chemicals (EDCs) which interfere with any hormonal aspect. The aim of the review was 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. It was also to present 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, how these mechanisms interact and sex specificities is 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

Environmental Pollutants and Metabolic Disorders: The Multi-Exposure Scenario of Life

International audienc