scholarly journals Multi-Systemic Alterations by Chronic Exposure to a Low Dose of Bisphenol A in Drinking Water: Effects on Inflammation and NAD+-Dependent Deacetylase Sirtuin1 in Lactating and Weaned Rats

2021 ◽  
Vol 22 (18) ◽  
pp. 9666
Author(s):  
Antonietta Santoro ◽  
Marika Scafuro ◽  
Jacopo Troisi ◽  
Giuseppe Piegari ◽  
Paola Di Pietro ◽  
...  
Keyword(s):  
Drinking Water ◽  
Adipose Tissue ◽  
Bisphenol A ◽  
Inflammatory Cytokines ◽  
Chronic Exposure ◽  
Adult Life ◽  
Sirtuin 1 ◽  
Cerebral Ventricles ◽  
Histone Deacetylase 1 ◽  
Significant Difference

Bisphenol A (BPA) is largely used as a monomer in some types of plastics. It accumulates in tissues and fluids and is able to bypass the placental barrier, affecting various organs and systems. Due to huge developmental processes, children, foetuses, and neonates could be more sensitive to BPA-induced toxicity. To investigate the multi-systemic effects of chronic exposure to a low BPA dose (100 μg/L), pregnant Wistar rats were exposed to BPA in drinking water during gestation and lactation. At weaning, newborn rats received the same treatments as dams until sex maturation. Free and conjugated BPA levels were measured in plasma and adipose tissue; the size of cerebral ventricles was analysed in the brain; morpho-functional and molecular analyses were carried out in the liver with a focus on the expression of inflammatory cytokines and Sirtuin 1 (Sirt1). Higher BPA levels were found in plasma and adipose tissue from BPA treated pups (17 PND) but not in weaned animals. Lateral cerebral ventricles were significantly enlarged in lactating and weaned BPA-exposed animals. In addition, apart from microvesicular steatosis, liver morphology did not exhibit any statistically significant difference for morphological signs of inflammation, hypertrophy, or macrovesicular steatosis, but the expression of inflammatory cytokines, Sirt1, its natural antisense long non-coding RNA (Sirt1-AS LncRNA) and histone deacetylase 1 (Hdac1) were affected in exposed animals. In conclusion, chronic exposure to a low BPA dose could increase the risk for disease in adult life as a consequence of higher BPA circulating levels and accumulation in adipose tissue during the neonatal period.

scholarly journals The effect of adipocyte–macrophage crosstalk in obesity-related breast cancer

2019 ◽  
Vol 62 (3) ◽  
pp. R201-R222 ◽  
Author(s):  
Ayse Basak Engin ◽  
Atilla Engin ◽  
Ipek Isik Gonul
Keyword(s):  
Breast Cancer ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Cancer Cells ◽  
Inflammatory Cytokines ◽  
Breast Cancer Cells ◽  
Sirtuin 1 ◽  
Aromatase Activity ◽  
Breast Adipose Tissue ◽  
Mtorc1 Signaling

Adipose tissue is the primary source of many pro-inflammatory cytokines in obesity. Macrophage numbers and pro-inflammatory gene expression are positively associated with adipocyte size. Free fatty acid and tumor necrosis factor-α involve in a vicious cycle between adipocytes and macrophages aggravating inflammatory changes. Thereby, M1 macrophages form a characteristic ‘crown-like structure (CLS)’ around necrotic adipocytes in obese adipose tissue. In obese women, CLSs of breast adipose tissue are responsible for both increase in local aromatase activity and aggressive behavior of breast cancer cells. Interlinked molecular mechanisms between adipocyte–macrophage–breast cancer cells in obesity involve seven consecutive processes: Excessive release of adipocyte- and macrophage-derived inflammatory cytokines, TSC1–TSC2 complex–mTOR crosstalk, insulin resistance, endoplasmic reticulum (ER) stress and excessive oxidative stress generation, uncoupled respiration and hypoxia, SIRT1 controversy, the increased levels of aromatase activity and estrogen production. Considering elevated risks of estrogen receptor (E2R)-positive postmenopausal breast cancer growth in obesity, adipocyte–macrophage crosstalk is important in the aforementioned issues. Increased mTORC1 signaling in obesity ensures the strong activation of oncogenic signaling in E2Rα-positive breast cancer cells. Since insulin and insulin-like growth factors have been identified as tumor promoters, hyperinsulinemia is an independent risk factor for poor prognosis in breast cancer despite peripheral insulin resistance. The unpredictable effects of adipocyte-derived leptin–estrogen–macrophage axis, and sirtuin 1 (SIRT1)–adipose-resident macrophage axis in obese postmenopausal patients with breast cancer are unresolved mechanistic gaps in the molecular links between the tumor growth and adipocytokines.

scholarly journals Microbial Metabolites of Gallotannins Suppress Inflammation in RAW 264.7 Macrophages Through the Modulation of the AMPK/NF-kb Axis

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 375-375
Author(s):  
Maria Castellon Chicas ◽  
Chuo Fang ◽  
Stephen Talcott ◽  
Susanne Talcott
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Sirtuin 1 ◽  
Separate Experiment ◽  
Raw 264.7 ◽  
Microbial Metabolites ◽  
Raw 264.7 Macrophages ◽  
Compound C ◽  
Gene And Protein Expression

Abstract Objectives Obesity has been positively correlated with alterations in adipose tissue such as increased production of pro-inflammatory molecules and high content of adipose tissue macrophages. In previous in vitro studies, we have shown that microbial metabolites of gallotannins (GT), including gallic acid (GA) and pyrogallol (PG), possess anti-inflammatory activities in cancer cells, as well as anti-lipogenic activities in adipocytes. In this study, we explored the molecular mechanisms of microbial metabolites of GT by investigating the effect of GA and PG on the inflammatory cytokines expression, AMP-activated protein kinase (AMPK) and NF-kb signaling pathways in RAW 264.7 macrophages. Methods RAW 264.7 macrophages were pre-treated with GA or PG (2.5 and 5 mg/L). Afterwards, inflammation was induced by 1 mg/mL lipopolysaccharide (LPS) along with the previous treatment. In a separate experiment, RAW 264.7 cells were pre-treated with or without 10 mM Compound C, an AMPK activity inhibitor, along with GA or PG (5 mg/L) and incubated with 1 mg/mL LPS. Analyses of gene and protein expression of inflammatory cytokines, AMPK and NF-kb were performed using qPCR and Western blot. Results mRNA and protein expressions of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) were significantly decreased in LPS-treated RAW 264.7 macrophages by GA and PG. Additionally, GA and PG inhibited LPS-induced inflammation through the up-regulation of AMPK and sirtuin 1 (Sirt1) activities, and the down-regulation of NF-kb activity. AMPK inhibition by Compound C in RAW 264.7 macrophages partially blocked LPS-induced inflammatory signaling. As a result, the inhibitory effects of GA and PG on LPS-induced inflammation were weakened. Conclusions GA and PG attenuate inflammation in RAW 264.7 macrophages at least in part through the activation of the AMPK pathway and the suppression of NF-kb activity. Overall, microbial metabolites of GT might possess therapeutic potential in the prevention of obesity-related adipose tissue inflammation. Funding Sources COALS's Nutrition Obesity Strategic Fellowship at Texas A&M University.

scholarly journals Overexpression of Activated AMPK in the Anopheles stephensi Midgut Impacts Mosquito Metabolism, Reproduction and Plasmodium Resistance

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 119
Author(s):  
Chioma Oringanje ◽  
Lillian R. Delacruz ◽  
Yunan Han ◽  
Shirley Luckhart ◽  
Michael A. Riehle
Keyword(s):  
Egg Production ◽  
Anopheles Stephensi ◽  
Mitochondrial Dynamics ◽  
Adult Life ◽  
Blood Feeding ◽  
Pathogen Resistance ◽  
Α Subunit ◽  
Significant Difference ◽  
Transgenic Lines ◽  
Ampk Activity

Mitochondrial integrity and homeostasis in the midgut are key factors controlling mosquito fitness and anti-pathogen resistance. Targeting genes that regulate mitochondrial dynamics represents a potential strategy for limiting mosquito-borne diseases. AMP-activated protein kinase (AMPK) is a key cellular energy sensor found in nearly all eukaryotic cells. When activated, AMPK inhibits anabolic pathways that consume ATP and activates catabolic processes that synthesize ATP. In this study, we overexpressed a truncated and constitutively active α-subunit of AMPK under the control of the midgut-specific carboxypeptidase promotor in the midgut of female Anopheles stephensi. As expected, AMPK overexpression in homozygous transgenic mosquitoes was associated with changes in nutrient storage and metabolism, decreasing glycogen levels at 24 h post-blood feeding when transgene expression was maximal, and concurrently increasing circulating trehalose at the same time point. When transgenic lines were challenged with Plasmodium falciparum, we observed a significant decrease in the prevalence and intensity of infection relative to wild type controls. Surprisingly, we did not observe a significant difference in the survival of adult mosquitoes fed either sugar only or both sugar and bloodmeals throughout adult life. This may be due to the limited period that the transgene was activated before homeostasis was restored. However, we did observe a significant decrease in egg production, suggesting that manipulation of AMPK activity in the mosquito midgut resulted in the re-allocation of resources away from egg production. In summary, this work identifies midgut AMPK activity as an important regulator of metabolism, reproduction, and innate immunity in An. stephensi, a highly invasive and important malaria vector species.

scholarly journals PSV-6 Effects of chilled drinking water and cooled floor pads on behavior of lactating sows under heat stress

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 153-154
Author(s):  
Yuzhi Li ◽  
Yunhui Zhu ◽  
Michael Reese ◽  
Eric Buchanan ◽  
Lee Johnston
Keyword(s):  
Drinking Water ◽  
Heat Stress ◽  
Time Budget ◽  
Calculated Data ◽  
Video Recordings ◽  
Significant Difference ◽  
Lactating Sows ◽  
Effect Of Treatment ◽  
Drinking Frequency ◽  
And Control

Abstract This study was conducted to evaluate effects of chilled drinking water and cooled floor pads on behavior of lactating sows under heat stress. Sows were housed in individual farrowing stalls in two rooms with temperatures being controlled at 29.4°C (0700h to 1900h) and 23.9°C (1900h to 0700h). Sows in one room (treatment), but not in the other room (control) were provided with chilled drinking water (13 to 15°C) and cooled floor pads (15 to 18°C). Behavior of sows (n=15 sows/treatment; parity=1 to 6) was video recorded during farrowing, and d 1, 3, 7, 14, and 21 after farrowing. Videos were viewed to register birth time of each piglet. Number of drinking bouts and duration of each bout were registered for 2 h (1530h to 1730h) each day after farrowing. Postures (lying laterally, lying ventrally, sitting, and standing) were recorded by scanning video-recordings at 5-min intervals for 24 h each day after farrowing, and time budget for each posture was calculated. Data were analyzed using the Glimmix Procedure of SAS. No effect of treatment was detected for litter size born, farrowing duration, or birth interval (P >0.33; Table 1). Neither frequency nor duration of drinking bouts was affected by treatment (P >0.27). No significant difference was observed in time budget for each posture (P >0.46) between treatment and control groups. As lactation progressed, sows increased drinking frequency (from 1.2 drinks/2h on d 1 to 4.9 drinks/2h on d 21; P< 0.001) and time spent lying ventrally (8% to 14%; P< 0.0001), standing (4% to 10%; P< 0.001), and sitting (2% to 4%; P< 0.0001), and decreased time spent lying laterally (86% to 67%; P< 0.0001) in both control and treatment rooms. These results indicate that chilled drinking water and cooled floor pads did not affect behavior of sows during farrowing and lactation in the current study.

scholarly journals Regional muscle-adipose distribution is different in patients with heart failure with preserved or reduced ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Ishikawa ◽  
Y Izumiya ◽  
A Shibata ◽  
T Yoshida ◽  
H Hayashi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Mass Index ◽  
Adipose Tissue ◽  
Ejection Fraction ◽  
Exercise Capacity ◽  
Exercise Tolerance ◽  
The Other ◽  
Reduced Ejection Fraction ◽  
Significant Difference ◽  
Regional Muscle

Abstract Background Epicardial adipose tissue (EAT) has been recognized to contribute inflammatory activity and atherosclerosis. On the other hand, it has been reported that the volume of EAT is lower in non-ischemic heart failure (HF) patients than healthy individuals. However, the difference in regional muscle-adipose distribution including EAT between HF with preserved ejection fraction (HFpEF) and HF reduced ejection fraction (HFrEF) has not been investigated. In addition, we investigated whether distribution of body composition contributed to exercise capacity. Methods The study included 105 non-ischemic HF patients diagnosed by cardiac catheterization between September 2017 and November 2019. Epicardial, abdominal and thigh muscle and adipose tissue volume were measured by computed tomography (CT), and exercise tolerance was evaluated by symptom-limited cardiopulmonary exercise test. Results Patients were divided into 2 groups according to the left ventricular ejection fraction, ≥40% as HFpEF (n=28) or <40% as HFrEF (n=77). There was no significant difference comorbidity, including hypertension, dyslipidemia, chronic kidney disease, and body mass index. Plasma B-type natriuretic peptide level was significantly higher in HFrEF than HFpEF group (146.2 vs 393.2 pg/ml, p<0.01), whereas, high-sensitive troponin T level was not different between two groups. Although there was no significant difference in BMI between two groups, the volume of EAT was significantly higher in HFpEF than HFrEF group (81.8 vs 136.4 ml, p=0.01). On the other hand, HFpEF had more thigh adipose tissue compared with HFrEF group (54.6 vs 42.1 ml, p=0.03). There were negative correlations between EAT volume and parameters of exercise capacity such as anaerobic threshold (r=−0.42, p<0.01) and peak VO2 (r=−0.32, p<0.01). Muscle volume itself does not corelate with these parameters. Conclusion In patient with nonischemic HF, the pattern of regional adipose distribution may have important role in pathologically. HFpEF and HFrEF has different pattern despite similar body mass index. These differences may be related to impaired exercise tolerance in these 2 different types of HF. Correlation between EAT and AT, peak VO2 Funding Acknowledgement Type of funding source: None

Is the child at risk? Cardiovascular remodelling in children born to diabetic mothers

2019 ◽  
Vol 29 (4) ◽  
pp. 467-474 ◽  
Author(s):  
Zahra Hoodbhoy ◽  
Nuruddin Mohammed ◽  
Nadeem Aslam ◽  
Urooj Fatima ◽  
Salima Ashiqali ◽  
...  
Keyword(s):  
Diastolic Function ◽  
Vascular Function ◽  
Adult Life ◽  
In Utero ◽  
University Hospital ◽  
Dietary Control ◽  
Significant Difference ◽  
Systolic And Diastolic Function ◽  
And Function ◽  
Diabetic Mothers

AbstractObjective:The objective of this study was to assess differences in myocardial systolic and diastolic function and vascular function in children 2−5 years of age born to diabetic as compared to non-diabetic mothers.Methods:This study was a retrospective cohort conducted in 2016 at The Aga Khan University Hospital, Karachi, Pakistan. It included children between 2 and 5 years of age born to mothers with and without exposure to diabetes in utero (n = 68 in each group) and who were appropriate for gestational age. Myocardial morphology and function using echocardiogram and carotid intima media thickness (cIMT) and pulse wave velocity was performed to evaluate cardiac function as well as macrovascular remodelling in these children. Multiple linear regression was used to compare the groups.Results:There was no significant difference in cardiac morphology, myocardial systolic and diastolic function, and macrovascular assessment between the exposed and unexposed groups of AGA children. Subgroup analysis demonstrated a significantly decreased mitral E/A ratio in children whose mothers were on medications as compared to those on dietary control (median [IQR] = 1.7 [1.6–1.9] and 1.56 [1.4–1.7], respectively, p = 0.02), and a higher cIMT in children whose mothers were on medication as compared to controls (0.48 [0.44–0.52] and 0.46 [0.44–0.50], respectively, p = 0.03).Conclusion:In utero exposure to uncontrolled maternal diabetes has an effect on the cardiovascular structure and function in children aged 2−5 years. However, future work requires long-term follow-up from fetal to adult life to assess these changes over the life course.

scholarly journals Effects of Physiological Hypercortisolemia on the Regulation of Lipolysis in Subcutaneous Adipose Tissue1

1998 ◽  
Vol 83 (2) ◽  
pp. 626-631 ◽  
Author(s):  
Jaswinder S. Samra ◽  
Mo L. Clark ◽  
Sandy M. Humphreys ◽  
Ian A. MacDonald ◽  
Peter A. Bannister ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Sodium Succinate ◽  
Hormone Sensitive Lipase ◽  
Whole Body ◽  
Constant Infusion ◽  
Nonesterified Fatty Acid ◽  
Significant Difference ◽  
Hormone Sensitive ◽  
Subcutaneous Adipose

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused iv to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 ± 100 vs. 335± 25 nmol/L; P < 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the sc adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of[ 1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P < 0.01) and blood glycerol concentrations (P < 0.05), with an increase in systemic glycerol appearance (P < 0.05). However, in sc abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05). This reduction was attributable to decreased intracellular lipolysis (P < 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P < 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.

scholarly journals Neonatal nutritional programming impairs adiponectin effects on energy homeostasis in adult life of male rats

2018 ◽  
Vol 315 (1) ◽  
pp. E29-E37 ◽  
Author(s):  
Mariana Peduti Halah ◽  
Paula Beatriz Marangon ◽  
Jose Antunes-Rodrigues ◽  
Lucila L. K. Elias
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Adult Life ◽  
Male Rats ◽  
Nutritional Programming

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

scholarly journals Identification of Nesfatin-1 in Human and Murine Adipose Tissue: A Novel Depot-Specific Adipokine with Increased Levels in Obesity

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3169-3180 ◽  
Author(s):  
Manjunath Ramanjaneya ◽  
Jing Chen ◽  
James E. Brown ◽  
Gyanendra Tripathi ◽  
Manfred Hallschmid ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Expression ◽  
Food Deprivation ◽  
Inflammatory Cytokines ◽  
Energy Homeostasis ◽  
Culture Media ◽  
Nonesterified Fatty Acid ◽  
High Fat ◽  
Gene And Protein Expression ◽  
The Impact

Nesfatin-1 is a recently identified anorexigenic peptide derived from its precursor protein, nonesterified fatty acid/nucleobindin 2 (NUCB2). Although the hypothalamus is pivotal for the maintenance of energy homeostasis, adipose tissue plays an important role in the integration of metabolic activity and energy balance by communicating with peripheral organs and the brain via adipokines. Currently no data exist on nesfatin-1 expression, regulation, and secretion in adipose tissue. We therefore investigated NUCB2/nesfatin-1 gene and protein expression in human and murine adipose tissue depots. Additionally, the effects of insulin, dexamethasone, and inflammatory cytokines and the impact of food deprivation and obesity on nesfatin-1 expression were studied by quantitative RT-PCR and Western blotting. We present data showing NUCB2 mRNA (P < 0.001), nesfatin-1 intracellular protein (P < 0.001), and secretion (P < 0.01) were significantly higher in sc adipose tissue compared with other depots. Also, nesfatin-1 protein expression was significantly increased in high-fat-fed mice (P < 0.01) and reduced under food deprivation (P < 0.01) compared with controls. Stimulation of sc adipose tissue explants with inflammatory cytokines (TNFα and IL-6), insulin, and dexamethasone resulted in a marked increase in intracellular nesfatin-1 levels. Furthermore, we present evidence that the secretion of nesfatin-1 into the culture media was dramatically increased during the differentiation of 3T3-L1 preadipocytes into adipocytes (P < 0.001) and after treatments with TNF-α, IL-6, insulin, and dexamethasone (P < 0.01). In addition, circulating nesfatin-1 levels were higher in high-fat-fed mice (P < 0.05) and showed positive correlation with body mass index in human. We report that nesfatin-1 is a novel depot specific adipokine preferentially produced by sc tissue, with obesity- and food deprivation-regulated expression.

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