scholarly journals SUN-638 Perinatal DDE Exposure Disrupts Thermogenesis Early in Development

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Annalise vonderEmbse ◽  
Jason W Tong ◽  
Pamela J Lein ◽  
Michele La Merrill
Keyword(s):  
Body Weight ◽  
Area Under The Curve ◽  
Positive Association ◽  
Epidemiological Studies ◽  
Metabolic Phenotype ◽  
Infrared Analysis ◽  
Metabolic Dysfunction ◽  
Primary Metabolite ◽  
Brown Adipose ◽  
Cold Challenge

Abstract Numerous epidemiological studies have identified a positive association of exposure to the endocrine-disrupting pesticide dichlorodiphenyltrichloroethane (DDT) and its primary metabolite dichlorodiphenyldichloroethylene (DDE) with the risk of obesity. Of particular concern is the persistent metabolic dysfunction resulting from early life DDT and DDE exposures, evidenced as obesity, glucose intolerance, dyslipidemia, and impaired thermogenesis in adult rodents. However, little is known about the developmental timing and etiopathogenesis of this long-term DDT-related metabolic phenotype. This study aimed to address these knowledge gaps by evaluating endocrine phenotypes and thermogenic parameters at two postnatal (P) time points, P0 and P12, in C57BL/6J mice. Dams were orally gavaged with p,p’-DDT (1.7 mg/kg body weight [BW]), p,p’-DDE (1.31 mg/kg BW), or organic olive oil (vehicle) daily from gestational day (GD) 11.5-P0 or P5. Infrared analysis was then performed during a cold challenge. We further attempted to rescue the cold-challenged P12 mice by administering the β3-adrenergic receptor (AR)-agonist CL316,243 (CL), a direct stimulator of brown adipose (BAT) thermogenesis. At P0, area under the curve analysis revealed higher body temperatures in both males and females exposed to DDE compared to controls during the 9 min cold challenge. In addition, DDE-exposed females lost body heat at a significantly faster rate than sex-matched controls over the 9 min cold challenge. This occurred without any treatment-related differences in resting glucose, suprascapular BAT weight, or body weight for either sex at P0. To assess BAT-autonomous response to β3-AR stimulation during a cold challenge, P12 mice were exposed to the pharmacological β3-AR agonist, or PBS control in a 2x2 exposure design and suprascapular BAT temperature was evaluated via infrared analysis of the suprascapular surface at 10 min intervals. Blood glucose, BAT weight, and BW remained equivocal across all P12 treatment groups. However, BAT temperature was significantly decreased 10 min after cold- challenge in female P12 mice with perinatal DDE-exposure when compared to sex- and perinatal treatment-matched controls. This DDE effect among P12 female mice was rescued by CL. These data suggest that thermogenic dysfunction consequent to perinatal DDE exposure is detectable during postnatal development, well before the emergence of endocrine phenotypes. The CL rescue of the BAT thermogenic impairments observed after perinatal DDE exposure are consistent with DDE toxicities upstream in the β3-AR nerve circuitry. Additionally, the data highlight the emergence of an early postnatal sex divergence in DDE-related thermogenic dysfunction. We speculate that the effects of DDE on suprascapular BAT heat production result from prenatal alterations in sympathetic circuitry.

scholarly journals Excess perigestational folic acid exposure induces metabolic dysfunction in post-natal life

2015 ◽  
Vol 224 (3) ◽  
pp. 245-259 ◽  
Author(s):  
Elisa Keating ◽  
Ana Correia-Branco ◽  
João R Araújo ◽  
Manuela Meireles ◽  
Rita Fernandes ◽  
...  
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Body Weight Gain ◽  
Female Offspring ◽  
Metabolic Phenotype ◽  
High Dose ◽  
Metabolic Dysfunction ◽  
Sprague Dawley ◽  
Female Progeny ◽  
Insulin Resistant

The aim of this study was to understand whether high folic acid (HFA) exposure during the perigestational period induces metabolic dysfunction in the offspring, later in life. To do this, female Sprague–Dawley rats (G0) were administered a dose of folic acid (FA) recommended for pregnancy (control, C, 2 mg FA/kg of diet,n=5) or a high dose of FA (HFA, 40 mg FA/kg of diet,n=5). Supplementation began at mating and lasted throughout pregnancy and lactation. Body weight and food and fluid intake were monitored in G0 and their offspring (G1) till G1 were 13 months of age. Metabolic blood profiles were assessed in G1 at 3 and 13 months of age (3M and 13M respectively). Both G0 and G1 HFA females had increased body weight gain when compared with controls, particularly 22 (G0) and 10 (G1) weeks after FA supplementation had been stopped. G1 female offspring of HFA mothers had increased glycemia at 3M, and both female and male G1 offspring of HFA mothers had decreased glucose tolerance at 13M, when compared with matched controls. At 13M, G1 female offspring of HFA mothers had increased insulin and decreased adiponectin levels, and G1 male offspring of HFA mothers had increased levels of leptin, when compared with matched controls. In addition, feeding of fructose to adult offspring revealed that perigestational exposure to HFA renders female progeny more susceptible to developing metabolic unbalance upon such a challenge. The results of this work indicate that perigestational HFA exposure the affects long-term metabolic phenotype of the offspring, predisposing them to an insulin-resistant state.

scholarly journals Parental obesity programs pancreatic cancer development in offspring

2019 ◽  
Vol 26 (5) ◽  
pp. 511-523 ◽  
Author(s):  
Raquel Santana da Cruz ◽  
Johan Clarke ◽  
Ana Cristina P Curi ◽  
Aseel Al-Yawar ◽  
Lu Jin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Body Weight ◽  
Control Diet ◽  
Epidemiological Studies ◽  
Cancer Development ◽  
Separate Experiment ◽  
Metabolic Dysfunction ◽  
History Of ◽  
History Of Obesity ◽  
The Impact

Epidemiological studies suggest that timing of obesity onset – and underlying metabolic dysfunction – is important in determining pancreatic cancer rates: early and young adult abdominal overweight/obesity is more strongly associated with this cancer than obesity that develops later in life. Parental obesity and overweight are associated with metabolic dysfunction and obesity in their children. Here, we evaluated the impact of parental overweight on offspring’s susceptibility of pancreatic cancer using the P48Cre/+/KrasG12D/+ mouse model. Male mice were fed an obesity-inducing diet (OID) before conception and mated with females raised on a control diet (CO) to generate the offspring. In a separate experiment, pregnant dams were fed CO or OID throughout gestation. The resulting OID offspring from the maternal (OID-m) or paternal lineage (OID-p) were used to study body weight, metabolic parameters and pancreatic cancer development and for molecular analysis. Parental obesity increased offspring’s body weight at birth, weaning and in adulthood compared to CO, with gender- and genotype-specific differences. OID-p and OID-m offspring showed metabolic disorder and accelerated development of high-grade PanIN/PDAC. OID offspring also had higher rates of acinar-to-ductal reprogramming assessed by CPA1+/SOX9+-positive pancreatic cells. Levels of Tenascin C (TNC), an ECM glycoprotein shown to suppress apoptosis, were elevated in OID offspring, particularly females. In line with that, OID offspring displayed increased collagen content and decreased apoptosis in pancreatic lesions compared to CO. An ancestral history of obesity through either the paternal or maternal lineages increases offspring’s susceptibility to pancreatic cancer development.

scholarly journals Can sonographic features of microcalcification predict thyroid nodule malignancy? a prospective observational study

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Mehrdad Nabahati ◽  
Rahele Mehraeen ◽  
Zoleika Moazezi ◽  
Naser Ghaemian
Keyword(s):  
Thyroid Nodule ◽  
Roc Analysis ◽  
Thyroid Nodules ◽  
Area Under The Curve ◽  
Positive Association ◽  
Needle Aspiration ◽  
Northern Iran ◽  
Significant Positive Association ◽  
Irregular Margin ◽  
Benign Nodules

Abstract Background The aim of this study was to investigate the diagnostic accuracy of microcalcification, as well as its associated sonographic features, for prediction of thyroid nodule malignancy. We prospectively assessed the patients with thyroid nodule, who underwent ultrasound-guided fine-needle aspiration during 2017–2020 in Babol, northern Iran. The ultrasonographic characteristics of the nodules, as well as their cytological results, were recorded. We used regression analysis to evaluate the relation between sonographic findings and nodule malignancy. A receiver operator characteristics (ROC) analysis was also used to estimate the ability of ultrasound to predict the characteristic features of malignancy, as estimated by the area under the curve (AUC). Results Overall, 1129 thyroid nodules were finally included in the study, of which 452 (40%) had microcalcification. A significant positive association was found between nodule malignancy and microcalcification in both univariate (OR=3.626, 95% CI 2.258–5.822) and multivariable regression analyses (OR=1.878, 95% CI 1.095–3.219). In the nodules with microcalcification, significant positive relations were seen between malignancy and hypoechogenicity (OR=3.833, 95% CI 1.032–14.238), >5 microcalcification number (OR=3.045, 95% CI 1.328–6.982), irregular margin (OR=3.341, 95% CI 1.078–10.352), and lobulated margin (OR=5.727, 95% CI 1.934–16.959). The ROC analysis indicated that AUC for hypoechogenicity, >5 microcalcification number, irregular margin, and lobulated margin were 60%, 62%, 55%, and 60%, respectively, in predicting malignant thyroid nodules. Conclusion The findings indicated that microcalcification can be a potential predictor of thyroid nodule malignancy. Also, the presence of irregular or lobulated margins, multiple intranodular microcalcification (>5 microcalcifications), and/or hypoechogenicity can improve the ability of microcalcification in distinguishing malignant from benign nodules.

scholarly journals Effects of cadmium and monensin on renal and cardiac functions of mice subjected to subacute cadmium intoxication

2014 ◽  
Vol 7 (2) ◽  
pp. 111-115 ◽  
Author(s):  
Juliana Ivanova ◽  
Yordanka Gluhcheva ◽  
Sonja Arpadjan ◽  
Mariana Mitewa
Keyword(s):  
Body Weight ◽  
Glucose Level ◽  
Oral Treatment ◽  
Toxic Metal ◽  
Chelating Agent ◽  
Treated Group ◽  
Epidemiological Studies ◽  
Organ Weight ◽  
Cardiac Functions ◽  
Icr Mouse

ABSTRACT Cadmium (Cd) is a well-known nephrotoxic agent. Cd-induced renal dysfunction has been considered as one of the causes leading to the development of hypertension. The correlation between Cd concentration in blood and urine and cardiovascular diseases has been discussed in many epidemiological studies. A therapy with chelating agents is utilized for the treatment of toxic metal intoxication. Herein we present novel information indicating that monensin (applied as tetraethylammonium salt) is a promising chelating agent for the treatment of Cd-induced renal and cardiac dysfunction. The study was performed using the ICR mouse model. Adult ICR male mice were divided into three groups with six animals in each group: control (received distilled water and food ad libitum for 28 days); Cd-intoxicated (treated orally with 20 mg/kg b.w. Cd(II) acetate from day 1 to day 14 of the experimental protocol), and monensin treated group (intoxicated with Cd(II) acetate as described for the Cd-intoxicated group followed by oral treatment with 16 mg/kg b.w. tetraethylammonium salt of monensic acid for 2 weeks). Cd intoxication of the animals resulted in an increase of the organ weight/body weight indexes. Cd elevated significantly creatinine and glucose level in serum. Monensin treatment improved the organ weight/body weight ratios. The therapy of the Cd-intoxicated animals with monensin ameliorated the creatinine and glucose level in serum and decreased the concentration of the toxic metal ions in the heart and kidneys by 54 % and 64 %, respectively

scholarly journals Inactivation of the adrenergic receptor β2 disrupts glucose homeostasis in mice

2014 ◽  
Vol 221 (3) ◽  
pp. 381-390 ◽  
Author(s):  
Gustavo W Fernandes ◽  
Cintia B Ueta ◽  
Tatiane L Fonseca ◽  
Cecilia H A Gouveia ◽  
Carmen L Lancellotti ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
Mrna Levels ◽  
High Fat ◽  
Adaptive Thermogenesis ◽  
Brown Adipose ◽  
Similar Body

Three types of beta adrenergic receptors (ARβ1–3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse withArβ2knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (4 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of norepinephrine or dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and ofArβ1, andArβ3mRNA levels. In addition, ARβ2KO mice exhibit similar body weight, adiposity, fasting plasma glucose, cholesterol, and triglycerides when compared with WT controls, but exhibit marked fasting hyperinsulinemia and elevation in hepaticPepck(Pck1) mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and inducedUcp1expression in a manner similar to WT controls, exhibiting a similar body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting hyperglycemia as compared with WT controls despite very elevated insulin levels, but similar degrees of liver steatosis and hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold- and diet-induced adaptive thermogenesis but disrupts glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting hyperglycemia but similar liver structure and lipid profile to the WT controls.

scholarly journals Pharmacokinetics of Tenofovir in Breast Milk of Lactating Rhesus Macaques

2005 ◽  
Vol 49 (5) ◽  
pp. 2093-2094 ◽  
Author(s):  
Koen K. A. Van Rompay ◽  
Marta Hamilton ◽  
Brian Kearney ◽  
Norbert Bischofberger
Keyword(s):  
Body Weight ◽  
Breast Milk ◽  
Rhesus Macaques ◽  
Area Under The Curve ◽  
Subcutaneous Dose

ABSTRACT To study tenofovir transfer into milk, two lactating macaques were given a subcutaneous dose of tenofovir (30 mg/kg of body weight). Peak concentrations and area under the curve values of tenofovir in milk were ∼3 and ∼20% of those detected in serum, respectively.

scholarly journals Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Alena Pecinova ◽  
Zdenek Drahota ◽  
Jana Kovalcikova ◽  
Nikola Kovarova ◽  
Petr Pecina ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Respiratory Chain ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Epidemiological Studies ◽  
The Body ◽  
Oxygen Species ◽  
Brown Adipose ◽  
First Choice ◽  
Species Production

Metformin is widely prescribed as a first-choice antihyperglycemic drug for treatment of type 2 diabetes mellitus, and recent epidemiological studies showed its utility also in cancer therapy. Although it is in use since the 1970s, its molecular target, either for antihyperglycemic or antineoplastic action, remains elusive. However, the body of the research on metformin effect oscillates around mitochondrial metabolism, including the function of oxidative phosphorylation (OXPHOS) apparatus. In this study, we focused on direct inhibitory mechanism of biguanides (metformin and phenformin) on OXPHOS complexes and its functional impact, using the model of isolated brown adipose tissue mitochondria. We demonstrate that biguanides nonspecifically target the activities of all respiratory chain dehydrogenases (mitochondrial NADH, succinate, and glycerophosphate dehydrogenases), but only at very high concentrations (10−2–10−1 M) that highly exceed cellular concentrations observed during the treatment. In addition, these concentrations of biguanides also trigger burst of reactive oxygen species production which, in combination with pleiotropic OXPHOS inhibition, can be toxic for the organism. We conclude that the beneficial effect of biguanides should probably be associated with subtler mechanism, different from the generalized inhibition of the respiratory chain.

Positive Association Between the Lys198 Asn Polymorphism in the Endothelin-1 and Blood Pressure in Obese Japanese Subjects: Ohasama Study

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 714-714
Author(s):  
Tomohiro Katsuya ◽  
Takayoshi Ohkubo ◽  
Yuxiao Fu ◽  
Ichiro Tsuji ◽  
Kenichi Nagai ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Level ◽  
Positive Association ◽  
Epidemiological Studies ◽  
Buffy Coat ◽  
Baseline Characteristic ◽  
Endothelin 1 ◽  
Overweight People ◽  
Obese Subjects

P117 A recent report by Tiret et al. (Hypertension 33, 1999) revealed that a G/T polymorphism with an amino acid substitution (Lys to Asn) at codon 198 in the exon 5 of endothelin 1 gene (ET1) is associated with blood pressure in overweight people using two epidemiological studies, ECTIM and Glasgow Heart Scan Study. They suggested that G/T polymorphism strongly interacted with body mass index (BMI) in the determination of blood pressure levels. To examine the interaction among G/T polymorphism of ET1, BMI and blood pressure, we carried out an association study using a general population. Subjects (n=1,446) were recruited from Ohasama population, which is a cohort in a rural community of northern Japan. The research protocol was approved by the Institutional Review Board of the Tohoku University. DNA was extracted from the buffy coat of the participants using QIAamp DNA Blood Kit (Qiagen Inc.). G/T polymorphism of ET1 was determined by TaqMan PCR method, which is a powerful tool for semiautomatic genotype determination in a large number of samples. The frequency of T198 allele in Japanese (26%) was significantly higher than that in Caucasians (23%). The baseline characteristic (age, BMI, SBP, DBP, antihypertensive treatment) of all subjects was not significantly different according to the genotype of G/T polymorphism. In the obese subjects (≥25kg/m2), however, SBP and DBP were significantly associated with G/T polymorphism. Blood pressure level in the subjects carrying T198 allele was 2.6 mmHg in systolic (p<0.02) and 2.3 mmHg in diastolic (p<0.005) higher than that in those with GG genotype in overweight people. That the same result was obtained from different races suggested that the T198 allele of ET1 is involved in the determination of blood pressure levels in obese subjects.

Brown adipose tissue activation in a rat model of Parkinson’s disease

2017 ◽  
Vol 313 (6) ◽  
pp. E731-E736 ◽  
Author(s):  
Wenjuan Wang ◽  
Xiangzhi Meng ◽  
Chun Yang ◽  
Dongliang Fang ◽  
Xuemeng Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Weight Loss ◽  
Body Weight ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Energy Intake ◽  
Rat Model ◽  
Sympathetic Denervation ◽  
Brown Adipose

Loss of body weight and fat mass is one of the nonmotor symptoms of Parkinson’s disease (PD). Weight loss is due primarily to reduced energy intake and increased energy expenditure. Whereas inadequate energy intake in PD patients is caused mainly by appetite loss and impaired gastrointestinal absorption, the underlying mechanisms for increased energy expenditure remain largely unknown. Brown adipose tissue (BAT), a key thermogenic tissue in humans and other mammals, plays an important role in thermoregulation and energy metabolism; however, it has not been tested whether BAT is involved in the negative energy balance in PD. Here, using the 6-hydroxydopamine (6-OHDA) rat model of PD, we found that the activity of sympathetic nerve (SN), the expression of Ucp1 in BAT, and thermogenesis were increased in PD rats. BAT sympathetic denervation blocked sympathetic activity and decreased UCP1 expression in BAT and attenuated the loss of body weight in PD rats. Interestingly, sympathetic denervation of BAT was associated with decreased sympathetic tone and lipolysis in retroperitoneal and epididymal white adipose tissue. Our data suggeste that BAT-mediated thermogenesis may contribute to weight loss in PD.

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