Effects of an environmentally relevant mixture of organochlorine pesticide compounds on adipogenesis and adipocyte function in an immortalized human adipocyte model.

Exposure to persistent organic pollutants (POPs), including organochlorine (OC) pesticide POPs, has been associated with the increased prevalence of obesity and type 2 diabetes. However, the underlying mechanisms through which exposure to these compounds may promote obesity and metabolic dysfunction remain an area of active investigation. To this end, the concentration dependent effects of an environmentally relevant mixture of OC pesticide POPs on adipocyte function was explored utilizing a translationally relevant immortalized human subcutaneous preadipocyte/adipocyte model.

Exposure to emulsified isoflurane and sevoflurane protects canine primary hepatocytes against hypoxia-induced apoptosis.

Objective: Emulsified isoflurane and sevoflurane have immunomodulating and anti-inflammatory effects in vital organs such as the brain, myocardium, and kidneys subjected to ischemia-reperfusion injury. This study aims to investigate the cellular protective effects of both emulsified anesthetics in cultured canine hepatocytes.

Procedures: We analyzed the apoptosis and viability responses of cultured primary canine hepatocytes exposed to 1% O2 for 30 versus 120 minutes after being treated with emulsified isoflurane or sevoflurane in 10% lipid, or 10% lipid alone or no-treatment control at 24 hours of reoxygenation (21% O2).

Alterations of Systemic and Hepatic Metabolic Function Following Exposure to Trans-nonachlor in Low and High Fat Diet Fed Male Sprague Dawley Rats.

The overall prevalence of metabolic diseases such as type 2 diabetes (T2D) and associated co-morbidities have increased at an alarming rate in the United States and worldwide. There is a growing body of epidemiological evidence implicating exposure to persistent organic pollutants (POPs), including legacy organochlorine (OC) pesticides and their bioaccumulative metabolites, in the pathogenesis of metabolic diseases. Therefore, the goal of the present study was to determine if exposure to trans-nonachlor, a bioaccumulative OC pesticide contaminant, in concert with high fat diet intake induced metabolic dysfunction.

Obesity II: Establishing causal links between chemical exposures and obesity.

Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens.

I21: an advanced high-resolution resonant inelastic X-ray scattering beamline at Diamond Light Source.

The I21 beamline at Diamond Light Source is dedicated to advanced resonant inelastic X-ray scattering (RIXS) for probing charge, orbital, spin and lattice excitations in materials across condensed matter physics, applied sciences and chemistry. Both the beamline and the RIXS spectrometer employ divergent variable-line-spacing gratings covering a broad energy range of 280-3000 eV. A combined energy resolution of ∼35 meV (16 meV) is readily achieved at 930 eV (530 eV) owing to the optimized optics and the mechanics.

Effect of high fat diet on the toxicokinetics and toxicodynamics of chlorpyrifos following acute exposure in male C57BL/6J mice.

Chlorpyrifos (CPS) is one of the most widely used organophosphate (OP) insecticides. The acute neurotoxicity of OPs results from the inhibition of acetylcholinesterase (AChE). However, some OPs also inhibit noncholinergic targets including monoacylglycerol lipase (MAGL), fatty acid amide hydrolase (FAAH), and carboxylesterase (CES).

Effects of chlorpyrifos on non-cholinergic toxicity endpoints in immortalized and primary rat hepatocytes under normal and hepatosteatotic conditions.

Chlorpyrifos (CPS) is the most widely used organophosphate (OP) insecticide. Non-cholinergic targets of OPs include enzymes belonging to the serine hydrolase family. Carboxylesterases (Ces) are involved in detoxication of xenobiotics as well as lipid metabolism in the liver.

Improving Readiness: Preventive Maintenance of the Human Operating System that Drives Readiness and Lethality.

Improving the readiness and lethality of the U.S. fighting forces has always been a key priority, and it received renewed emphasis in the National Defense Authorization Act of 2017.

Dosage scaling of alcohol in binge exposure models in mice: An empirical assessment of the relationship between dose, alcohol exposure, and peak blood concentrations in humans and mice.

Binge drinking is a remarkably prevalent behavior. In 2015, 27% of U.S.

Alterations in macrophage phagocytosis and inflammatory tone following exposure to the organochlorine compounds oxychlordane and trans-nonachlor.

The role of macrophages in the innate immune response cannot be underscored however recent studies have demonstrated that both resident and recruited macrophages have critical roles in the pathogenesis of metabolic dysfunction. Given the recent data implicating exposure to persistent organic pollutants (POPs) in the pathogenesis of metabolic diseases, the current study was designed to examine the effects of the highly implicated organochlorine (OC) compounds oxychlordane and trans-nonachlor on overall macrophage function. Murine J774A.

Persistent organic pollutants (POPs) increase rage signaling to promote downstream cardiovascular remodeling.

Exposure to environmental contaminants and consumption of a high, saturated fatty diet has been demonstrated to promote precursors for metabolic syndrome (hyperglycemia, hyperinsulinemia, and hypertriglyceridemia). The purpose of this study was to determine if exposure to the most prevalent environmental persistent organic pollutants (POPs) would act as causative agents to promote metabolic syndrome independent of dietary intake. We hypothesized that POPs will activate the advanced glycated end-product (AGE)-and receptor for AGE (RAGE) signaling cascade to promote downstream signaling modulators of cardiovascular remodeling and oxidative stress in the heart.

Alterations in cellular lipid metabolism produce neutral lipid accumulation following exposure to the organochlorine compound trans-nonachlor in rat primary hepatocytes.

Recent epidemiological studies have revealed significant positive associations between exposure to organochlorine (OC) pesticides and occurrence of the metabolic syndrome and there are a growing number of animal-based studies to support causality. However, the cellular mechanisms linking OC compound exposure and metabolic dysfunction remain elusive. Therefore, the present study was designed to determine if direct exposure to three highly implicated OC compounds promoted hepatic steatosis, the hepatic ramification of the metabolic syndrome.

Inhibition of cholinergic and non-cholinergic targets following subacute exposure to chlorpyrifos in normal and high fat fed male C57BL/6J mice.

The effects of obesity on organophosphate pesticide-mediated toxicities, including both cholinergic and non-cholinergic targets, have not been fully elucidated. Therefore, the present study was designed to determine if high fat diet intake alters the effects of repeated exposure to chlorpyrifos (CPS) on the activities of both cholinergic and noncholinergic serine hydrolase targets. Male C57BL/6J mice were placed on either standard rodent chow or high fat diet for four weeks with CPS exposure (2.

"Trans-nonachlor increases extracellular free fatty acid accumulation and de novo lipogenesis to produce hepatic steatosis in McArdle-RH7777 cells".

Recent studies suggest there may be an environmental exposure component to the development and progression of non-alcoholic fatty liver disease (NAFLD) involving the organochlorine (OC) pesticides or their metabolites. However, the roles of OC compounds in the development of NAFLD has not been fully elucidated. Therefore, the current study was designed to determine if exposure to trans-nonachlor, a prevalent OC compound, could promote hepatocyte lipid accumulation and determine potential pro-steatotic mechanisms.

Effects of acute exposure to chlorpyrifos on cholinergic and non-cholinergic targets in normal and high-fat fed male C57BL/6J mice.

The prevalence of obesity is increasing at an alarming rate in the United States with 36.5% of adults being classified as obese. Compared to normal individuals, obese individuals have noted pathophysiological alterations which may alter the toxicokinetics of xenobiotics and therefore alter their toxicities.

Exposure to an environmentally relevant mixture of organochlorine compounds and polychlorinated biphenyls Promotes hepatic steatosis in male Ob/Ob mice.

Hepatic steatosis is recognized as an independent risk factor for the development of cardiovascular disease. While obesity and type 2 diabetes are well-established risk factors in the development of hepatic steatosis, recent studies have revealed exposure to mixtures of persistent organic pollutants (POPs), which are environmental contaminants in various fatty foods, can promote steatosis. Thus, the present study was designed to determine if exposure to a defined mixture of prevalent polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides or their metabolites promote hepatic steatosis in a genetically induced model of type 2 diabetes, the leptin-deficient ob/ob mouse.

Exposure to chlorpyrifos increases neutral lipid accumulation with accompanying increased de novo lipogenesis and decreased triglyceride secretion in McArdle-RH7777 hepatoma cells.

Hepatic steatosis is associated with hepatic insulin resistance as well as hypertriglyceridemia. Recent studies have determined exposure to organophosphate (OP) pesticides can cause dyslipidemia and hepatic steatosis. However, the mechanisms through which OPs induced hepatic steatosis are not completely understood.

Exposure to p,p'-DDE Alters Macrophage Reactivity and Increases Macrophage Numbers in Adipose Stromal Vascular Fraction.

Exposure to p,p'-DDE (DDE), the main bioaccumulative metabolite of the organochlorine insecticide p,p'-DDT, is associated with a higher prevalence of obesity, dyslipidemia, insulin resistance, metabolic syndrome, and immunomodulation. The present study was carried out to determine whether DDE perturbs adipose tissue homeostasis through modulation of macrophage function. Treatment with DDE or a cyclooxygenase-2 inhibitor prior to lipopolysaccharide exposure significantly decreased production of prostaglandins (PG) from J774a.

Exposure to p,p'-DDE enhances differentiation of 3T3-L1 preadipocytes in a model of sub-optimal differentiation.

The incidence of obesity is increasing worldwide at an alarming rate. Recently, exposure to environmental contaminants, especially organochlorines such as p,p'-dichlorodiphenyldichloroethylene (DDE), has been implicated as a possible causative factor in the increasing obesity epidemic. The objective of this study was to evaluate the ability of DDE to alter adipogenesis in a model of sub-optimal differentiation.

I12: the Joint Engineering, Environment and Processing (JEEP) beamline at Diamond Light Source.

I12 is the Joint Engineering, Environmental and Processing (JEEP) beamline, constructed during Phase II of the Diamond Light Source. I12 is located on a short (5 m) straight section of the Diamond storage ring and uses a 4.2 T superconducting wiggler to provide polychromatic and monochromatic X-rays in the energy range 50-150 keV.

Effect of chronic p,p'-dichlorodiphenyldichloroethylene (DDE) exposure on high fat diet-induced alterations in glucose and lipid metabolism in male C57BL/6H mice.

Diabetes mellitus is a highly prevalent metabolic disease affecting 29.1 million people or 9.3% of the population of the United States.

Exposure to p,p'-dichlorodiphenyldichloroethylene (DDE) induces fasting hyperglycemia without insulin resistance in male C57BL/6H mice.

Approximately 8.3% of the United States (U.S.

Exposure to bioaccumulative organochlorine compounds alters adipogenesis, fatty acid uptake, and adipokine production in NIH3T3-L1 cells.

Exposure to the organochlorine compounds p,p'-dichlorodiphenyldichloroethylene (DDE) and oxychlordane have been associated with an increased prevalence of diabetes. Although the exact etiology of diabetes, especially type 2 diabetes, is not known, it is thought that adipose dysfunction plays a vital role in the progression of this disease. Thus, the present study examined whether exposure to these bioaccumulative compounds promotes adipocyte dysfunction including alterations in adipogenesis, fatty acid storage, and adipokine production within the adipocyte.