Pubertal glyphosate-based herbicide exposure aggravates high-fat diet-induced obesity in female mice.

Glyphosate-based herbicides (GBH) are the most widely used pesticides globally. Studies have indicated that they may increase the risk of various organic dysfunctions. Herein, we verified whether exposure to GBH during puberty increases the susceptibility of male and female mice to obesity when they are fed a high-fat diet (HFD) in adulthood. From the 4th-7th weeks of age, male and female C57Bl/6 mice received water (CTL group) or 50 mg GBH /kg body weight (BW; GBH group). From the 8th-21st weeks of age, the mice were fed a standard diet or a HFD. It was found that pubertal GBH exposure exacerbated BW gains and hyperphagia induced by HFD, but only in female GBH-HFD mice. These female mice also exhibited high accumulation of perigonadal and subcutaneous fat, as well as reduced lean body mass. Both male and female GBH-HFD displayed hypertrophic white adipocytes. However, only in females, pubertal GBH exposure aggravated HFD-induced fat accumulation in brown adipocytes. Furthermore, GBH increased plasma cortisol levels by 80% in GBH-HFD males, and 180% in GBH-HFD females. In conclusion, pubertal GBH exposure aggravated HFD-induced obesity, particularly in adult female mice. This study provides novel evidence that GBH misprograms lipid metabolism, accelerating the development of obesity when individuals are challenged by a second metabolic stressor, such as an obesogenic diet.

The effect of long-term exposure to nonylphenol at environmentally relevant levels on mouse liver and adipose tissue.

Exposure to the xenoestrogen nonylphenol (NP) during critical windows of development leads to metabolic abnormalities in adult life. However, less is known about NP exposure outside the developmental period on metabolic outcomes. We investigated the effect of prolonged exposure to NP after sexual maturity and at environmentally relevant concentrations below the 'no observable adverse effects level' (0.5 and 2.5 mg/kg/d). Male Swiss mice fed a normal-fat diet exposed to 2.5 mg/kg/d NP showed reduced weight gain and hepatic fat content. In male and female C57BL/6 mice fed a high-fat diet, NP exposure modified the mRNA levels of estrogen receptor α (Esr1) and adipose lineage markers in a sexually dimorphic and adipose depot-dependent pattern. Moreover, in primary female but not male stromal vascular cells from C57BL/6 mouse inguinal WAT induced to differentiate into adipocytes, NP upregulated Fabp4 expression. Low-level exposure to NP outside critical developmental windows may affect the metabolic phenotype distinctly. DATA AVAILABILITY STATEMENT: All data not included in the manuscript, such as raw results, are available upon request and should be addressed to AAA.

Obesity and endocrine-disrupting chemicals.

Obesity is now a worldwide pandemic. The usual explanation given for the prevalence of obesity is that it results from consumption of a calorie dense diet coupled with physical inactivity. However, this model inadequately explains rising obesity in adults and in children over the past few decades, indicating that other factors must be important contributors. An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture that interferes with any aspect of hormone action. EDCs have become pervasive in our environment, allowing humans to be exposed daily through ingestion, inhalation, and direct dermal contact. Exposure to EDCs has been causally linked with obesity in model organisms and associated with obesity occurrence in humans. Obesogens promote adipogenesis and obesity, in vivo, by a variety of mechanisms. The environmental obesogen model holds that exposure to obesogens elicits a predisposition to obesity and that such exposures may be an important yet overlooked factor in the obesity pandemic. Effects produced by EDCs and obesogen exposure may be passed to subsequent, unexposed generations. This "generational toxicology" is not currently factored into risk assessment by regulators but may be another important factor in the obesity pandemic as well as in the worldwide increases in the incidence of noncommunicable diseases that plague populations everywhere. This review addresses the current evidence on how obesogens affect body mass, discusses long-known chemicals that have been more recently identified as obesogens, and how the accumulated knowledge can help identify EDCs hazards.

Developmental Exposure to the Flame Retardant Mixture Firemaster 550 Compromises Adult Bone Integrity in Male but not Female Rats.

Flame retardants (FRs) are used in a variety of common items from furniture to carpet to electronics to reduce flammability and combustion, but the potential toxicity of these compounds is raising health concerns globally. Organophosphate FRs (OPFRs) are becoming more prevalent as older, brominated FRs are phased out, but the toxicity of these compounds, and the FR mixtures that contain them, is poorly understood. Work in a variety of in vitro model systems has suggested that FRs may induce metabolic reprogramming such that bone density is compromised at the expense of increasing adiposity. To address this hypothesis, the present studies maternally exposed Wistar rat dams orally across gestation and lactation to 1000 µg daily of the FR mixture Firemaster 550 (FM 550) which contains a mixture of brominated FRs and OPFRs. At six months of age, the offspring of both sexes were examined for evidence of compromised bone composition. Bone density, composition, and marrow were all significantly affected, but only in males. The fact that the phenotype was observed months after exposure suggests that FM 550 altered some fundamental aspect of mesenchymal stem cell reprogramming. The severity of the phenotype and the human-relevance of the dose employed, affirm this is an adverse outcome meriting further exploration.

Overview of the Pathophysiological Implications of Organotins on the Endocrine System.

Organotins (OTs) are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic-pituitary axis), altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus) or peripheral (e.g., adipose tissue) mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed.

Effects of arsenic on adipocyte metabolism: Is arsenic an obesogen?

The environmental obesogen model proposes that in addition to a high-calorie diet and diminished physical activity, other factors such as environmental pollutants and chemicals are involved in the development of obesity. Although arsenic has been recognized as a risk factor for Type 2 Diabetes with a specific mechanism, it is still uncertain whether arsenic is also an obesogen. The impairment of white adipose tissue (WAT) metabolism is crucial in the onset of obesity, and distinct studies have evaluated the effects of arsenic on it, however only in some of them for obesity-related purposes. Thus, the known effects of arsenic on WAT/adipocytes were integrated based on the diverse metabolic and physiological processes that occur in WAT and are altered in obesity, specifically: adipocyte growth, adipokine secretion, lipid metabolism, and glucose metabolism. The currently available information suggests that arsenic can negatively affect WAT metabolism, resulting in arsenic being a potential obesogen.