scholarly journals Sexual Dimorphism in Changes That Occur in Tissues, Organs and Plasma during the Early Stages of Obesity Development

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 717
Author(s):  
Priyanka Dhanraj ◽  
Marlene B. van Heerden ◽  
Michael S. Pepper ◽  
Melvin A. Ambele
Keyword(s):  
Weight Gain ◽  
Sexual Dimorphism ◽  
Macrophage Infiltration ◽  
Health Concern ◽  
Gm Csf ◽  
Early Stages ◽  
Cytokine Levels ◽  
Adipocyte Hypertrophy ◽  
Plasma Hormones ◽  
Clinical Changes

Despite obesity being a major health concern, information on the early clinical changes that occur in plasma and tissues during obesity development and the influence of sexual dimorphism is lacking. This study investigated changes in tissue and organ histology, macrophage infiltration, plasma hormones, lipid, and chemokine and cytokine levels in mice fed on a high fat diet for 11-weeks. An increase in adiposity, accompanied by adipocyte hypertrophy and macrophage infiltration, was observed to be significantly greater in males than females. Important changes in cell morphology and histology were noted in the lungs, liver, kidney, spleen, and heart, which may indicate early signs for developing obesity associated comorbidities. Leptin, but not adiponectin, was significantly altered during weight gain. Additionally, leptin, but not adiposity, correlated with insulin levels. Interestingly, GM-CSF, TNFα, and IL-12 (p70) were not produced in the early stages of obesity development. Meanwhile, the production of MCP-1, IP-10, RANTES, IL-10, IL-6, KC, and IL-9 were greatly influenced by sexual dimorphism. Importantly, IL-6/IL-10 axis of anti-inflammatory cytokine regulation was observed only in females and may account for their significantly lower weight gain compared to males. This study provides new knowledge on how sexual dimorphism may influence the development of obesity and associated comorbidities.

scholarly journals GM-CSF driven myeloid cells in adipose tissue link weight gain and insulin resistance via formation of 2-aminoadipate

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Deanna L. Plubell ◽  
Alexandra M. Fenton ◽  
Phillip A. Wilmarth ◽  
Paige Bergstrom ◽  
Yuqi Zhao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Myeloid Cells ◽  
Gm Csf ◽  
Link Weight

scholarly journals Elevated antiviral, myeloid and endothelial inflammatory markers in severe COVID-19

2020 ◽  
Author(s):  
Ryan S Thwaites ◽  
Ashley Sanchez Sevilla Uruchurtu ◽  
Matthew Siggins ◽  
Felicity Liew ◽  
Clark D Russell ◽  
...  
Keyword(s):  
Lung Injury ◽  
Cell Activation ◽  
Vascular Inflammation ◽  
Endothelial Cell Activation ◽  
Gm Csf ◽  
Cytokine Levels ◽  
Angiopoietin 2 ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Host Inflammatory Response

Introductory paragraphThe mechanisms that underpin COVID-19 disease severity, and determine the outcome of infection, are only beginning to be unraveled. The host inflammatory response contributes to lung injury, but circulating mediators levels fall below those in classical ‘cytokine storms’. We analyzed serial plasma samples from 619 patients hospitalized with COVID-19 recruited through the prospective multicenter ISARIC clinical characterization protocol U.K. study and 39 milder community cases not requiring hospitalization. Elevated levels of numerous mediators including angiopoietin-2, CXCL10, and GM-CSF were seen at recruitment in patients who later died. Markers of endothelial injury (angiopoietin-2 and von-Willebrand factor A2) were detected early in some patients, while inflammatory cytokines and markers of lung injury persisted for several weeks in fatal COVID-19 despite decreasing antiviral cytokine levels. Overall, markers of myeloid or endothelial cell activation were associated with severe, progressive, and fatal disease indicating a central role for innate immune activation and vascular inflammation in COVID-19.

scholarly journals Inflammatory phenotyping predicts clinical outcome in COVID-19

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
H. Burke ◽  
◽  
A. Freeman ◽  
D. C. Cellura ◽  
B. L. Stuart ◽  
...  
Keyword(s):  
Adverse Outcome ◽  
Outcome Data ◽  
University Hospital ◽  
Clinical Parameters ◽  
Gm Csf ◽  
Poor Outcome ◽  
Hospitalised Patients ◽  
Cytokine Levels ◽  
Patients At Risk ◽  
Multiplex Cytokine

Abstract Background The COVID-19 pandemic has led to more than 760,000 deaths worldwide (correct as of 16th August 2020). Studies suggest a hyperinflammatory response is a major cause of disease severity and death. Identitfying COVID-19 patients with hyperinflammation may identify subgroups who could benefit from targeted immunomodulatory treatments. Analysis of cytokine levels at the point of diagnosis of SARS-CoV-2 infection can identify patients at risk of deterioration. Methods We used a multiplex cytokine assay to measure serum IL-6, IL-8, TNF, IL-1β, GM-CSF, IL-10, IL-33 and IFN-γ in 100 hospitalised patients with confirmed COVID-19 at admission to University Hospital Southampton (UK). Demographic, clinical and outcome data were collected for analysis. Results Age > 70 years was the strongest predictor of death (OR 28, 95% CI 5.94, 139.45). IL-6, IL-8, TNF, IL-1β and IL-33 were significantly associated with adverse outcome. Clinical parameters were predictive of poor outcome (AUROC 0.71), addition of a combined cytokine panel significantly improved the predictability (AUROC 0.85). In those ≤70 years, IL-33 and TNF were predictive of poor outcome (AUROC 0.83 and 0.84), addition of a combined cytokine panel demonstrated greater predictability of poor outcome than clinical parameters alone (AUROC 0.92 vs 0.77). Conclusions A combined cytokine panel improves the accuracy of the predictive value for adverse outcome beyond standard clinical data alone. Identification of specific cytokines may help to stratify patients towards trials of specific immunomodulatory treatments to improve outcomes in COVID-19.

scholarly journals Large Lemurs: Ecological, Demographic and Environmental Risk Factors for Weight Gain in Captivity

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1443
Author(s):  
Emma L. Mellor ◽  
Innes C. Cuthill ◽  
Christoph Schwitzer ◽  
Georgia J. Mason ◽  
Michael Mendl
Keyword(s):  
Risk Factors ◽  
Weight Gain ◽  
Environmental Risk ◽  
Food Resource ◽  
Potential Ecological Risk ◽  
Environmental Risk Factors ◽  
Health Concern ◽  
Wild Food ◽  
Future Research ◽  
In Captivity

Excessive body mass, i.e., being overweight or obese, is a health concern associated with issues such as reduced fertility and lifespan. Some lemur species are prone to extreme weight gain in captivity, yet others are not. To better understand species- and individual-level effects on susceptibility to captive weight gain, we use two complementary methods: phylogenetic comparative methods to examine ecological explanations for susceptibility to weight gain across species, and epidemiological approaches to examine demographic and environment effects within species. Data on body masses and living conditions were collected using a survey, yielding useable data on 675 lemurs representing 13 species from 96 collections worldwide. Data on species-typical wild ecology for comparative analyses came from published literature and climate databases. We uncovered one potential ecological risk factor: species adapted to greater wild food resource unpredictability tended to be more prone to weight gain. Our epidemiological analyses on the four best-sampled species revealed four demographic and one environmental risk factors, e.g., for males, being housed with only fixed climbing structures. We make practical recommendations to help address weight concerns, and describe future research including ways to validate the proxy we used to infer body condition.

Perigestational high folic acid: impact on offspring's peripheral metabolic response

2019 ◽  
Vol 10 (11) ◽  
pp. 7216-7226
Author(s):  
Ana Tojal ◽  
Catarina Neves ◽  
Hugo Veiga ◽  
Sílvia Ferreira ◽  
Ilda Rodrigues ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Folic Acid ◽  
Weight Gain ◽  
Metabolic Response ◽  
Adipocyte Hypertrophy

Perigestational excess folic acid programmed offspring to increased weight gain, but also to adipocyte hypertrophy, associated with Lpl upregulation, and to hyperglycemia, possibly due to VAT and skeletal muscle Glut4 downregulation.

Developing a predictive model for disease status in breast cancer patients using Th1 and Th2 serum cytokine profiles

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10078-10078 ◽  
Author(s):  
S. Khoo ◽  
T. Kao ◽  
Z. A. Dehqanzada ◽  
C. E. Storrer ◽  
K. A. Harris ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Predictive Value ◽  
Small Sample ◽  
Nodal Status ◽  
Outcome Variable ◽  
Breast Cancer Patients ◽  
Serum Cytokine ◽  
Gm Csf ◽  
Cytokine Levels ◽  
Potential Biomarkers

10078 Background: Using the Luminex multiplex assay, we have reported significant correlations between serum levels of MCP-1, eotaxin, and IL-6 and disease characteristics in breast cancer (BCa) patients. We now examine the potential of utilizing a general cytokine profile to develop a statistical model to predict certain disease states in these patients. Methods: Sera from 36 BCa patients (24 node-negative, 12 node-positive, 12 normals) were analyzed using the Luminex assay for levels of 21 cytokines (IL-1α, 1b, 2, 4, 5, 6, 8, 10, 12, 13, 15, 17, IFN-γ, G-CSF, GM-CSF, TNF-α, IP-10, MIP-1α, RANTES, MCP-1, eotaxin). Logistic regression models were used to assess if a binary outcome variable (Y) can be predicted by using serum cytokine levels (X). The area under a receiver operating characteristic (ROC) curve (c) was used to assess the potential utility of a biomarker. The larger the value of c, the better the biomarker. Results: MCP-1 was found to be a possible predictor of the presence of BCa while other potential biomarkers were IL-13, MIP-1α and eotaxin. The higher the MCP-1 level, the greater the likelihood that the patient would have BCa. Similar relationships applied to the other potential biomarkers. Among BCa patients, GM-CSF seemed to be a good predictor of nodal status with lower levels of GM-CSF predicting positive nodes. Other potential biomarkers with a similar expression pattern for nodal status were MCP-1, IL-6 and IL-5. Due to small sample sizes, we were unable to examine a potential “panel” of cytokines to develop a prognostic algorithm based on serum analysis. Conclusions: MCP-1, which was previously shown to be elevated in BCa, may also have some predictive value linking the presence of disease and disease severity as measured by nodal status. Other prominent cytokines from earlier studies (MIP-1α, eotaxin, IL-6) also displayed some possible predictive value. Our results warrant studying a larger population in order to establish a unified prognostic formula for BCa based on serum cytokine levels. [Table: see text] No significant financial relationships to disclose.

Predictive utility of serum cytokine levels in patients with metastatic renal cell carcinoma (MRCC) treated with interferon alfa (IFNa)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14503-14503
Author(s):  
A. J. Montero ◽  
C. Diaz-Montero ◽  
X. Wang ◽  
B. W. McIntyre ◽  
N. Tannir
Keyword(s):  
Clinical Outcome ◽  
Clinical Benefit ◽  
Serum Levels ◽  
Phase Iii ◽  
Gm Csf ◽  
Risk Of Death ◽  
Ifna Therapy ◽  
Increased Risk ◽  
Cytokine Levels ◽  
Th1 Cytokines

14503 Background: IFNa may prolong survival in MRCC patients (pts) due to stimulation of cell-mediated immunity. We hypothesized that IFNa exerts an anti-tumor effect by upregulation of Th1 cytokines and that patients (pts) with elevated serum levels of Th1 cytokines either at baseline (BL) or after treatment with IFNa would have a superior clinical outcome. Methods: Cytokine profiling was performed on 104 pts with MRCC treated in a randomized phase III trial with IFNa 0.5 million units (MU) subcutaneously (SC) twice daily or 5 MU SC daily. Serum samples were collected at BL (n = 104) and after 8 weeks of IFNa therapy (C1) (n = 89). Cytokine concentrations were determined using a 16-plex immunoassay. The linear mixed-effect model was fit to assess the change of cytokine levels from BL to C1. Cox proportional hazards model was fit to evaluate the effect of BL cytokine levels or change of cytokine levels from BL to C1 on the risk of death. Results: Of 16 cytokines evaluated (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p40, IL-13, IL-15, IL-17, IFNa, IFNg, GM-CSF, TNFa, VEGF), lower BL TNFa, IL-8 (Th1), and IL-13 (Th2) levels were associated with clinical benefit (major response or progression-free status at 6 months) (p = 0.01 and 0.03, respectively). By multivariate analysis, only extremely low or high levels of IFNa (p = 0.02) and IL-12 (p = 0.002) at BL were associated with an increased risk of death. IFNa therapy after C1 produced higher levels of several Th1 cytokines (IL-8, IL-12 p40, IL-15) (p < .001) and lower levels of Th2 cytokines (IL-4, IL-13). Unexpectedly, there were significantly lower levels of TNFa and GM-CSF (Th1) and higher levels of IL-10 (Th2) with IFNa. Only an increase of IL-2 levels from BL to C1 (RR 1.45; p = 0.05) correlated with an increased risk of death. Conclusions: Lower BL serum levels of TNFa, IL-8, and IL-13 were associated with clinical benefit to IFNa. Although IFNa therapy favored a shift towards a Th1 response, this effect alone did not correlate with clinical outcome. No significant financial relationships to disclose.

scholarly journals Correlations among parental and neonatal anthropometric parameters, feeding practices and infant obesity

2014 ◽  
Vol 87 (3) ◽  
pp. 166-170
Author(s):  
Daniel Sabau ◽  
Maria Stamatin ◽  
Silvia Stoicescu ◽  
Valeria Filip ◽  
Manuela Cucerea ◽  
...  
Keyword(s):  
Weight Gain ◽  
Birth Weight ◽  
Mode Of Delivery ◽  
Birth Trauma ◽  
Health Concern ◽  
Milk Formula ◽  
Study Group ◽  
First Feeding ◽  
Maternity Hospitals ◽  
Weight Gain During Pregnancy

Background and aims: Infant and adult obesity is becoming a real public health concern in Romania, similar to other countries of the European Union. Maternal obesity and excessive weight gain during pregnancy are proven risk factors for the obesity of the child. The protective role of the breastfeeding against obesity has also been demonstrated. The most important issue is whether the choice of a milk formula with the right protein composition could or not protect the newborn from becoming a future obese infant and child. Our study aims to describe the characteristics of a group of macrosomic newborns,in relation to the mothers’ weight gain during pregnancy, mode of delivery, birth weight, complications at birth, time of first feeding and type of feeding during maternity stay. Patients and methods: we conducted a retrospective study on 179 newborns with birth weights > 4000 grams, born over a period of three months (March-May) in 6 large maternity hospitals in Romania. Results: the newborns had a mean gestational age of 39.5 weeks and a mean birth weight of 4195 grams. Male newborns were prevalent (74%). More than half were born by Cesarian section and had Apgar scores with a median of 9. Macrosomes are prone to complications at birth and in our study those were mainly hypoglycemia and birth trauma. Time at first feeding was 95 minutes (mean), with a high percentage of formula/mixed feeding (68%). Conclusion: Macrosomia itself attracts the risk of birth by cesarean section (54% of study group), birth trauma and a low rate of exclusive breast milk feeding (32% of study group) at discharge.

scholarly journals Cytokine Secretions in Partial Breast Tumor Microenvironment With and Without Sulforaphane

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 274-274
Author(s):  
Courtney Merrick ◽  
Lauren Housley
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Treatment Options ◽  
Graduate Studies ◽  
Gm Csf ◽  
Funding Sources ◽  
Cytokine Levels ◽  
Vital Cell

Abstract Objectives Triple-negative breast cancer (TNBC) comprises 10–20% of breast cancer cases. It is particularly aggressive with limited and deleterious treatment options. Increasingly, research confirms that communication between cancer cells and neighboring macrophages promotes disease progression in part by secretion of cytokines that increase tumor cell proliferation, invasion, and metastasis. Sulforaphane (SFN) is a chemopreventive phytochemical found in cruciferous vegetables (broccoli) shown to alter cytokine secretion in macrophages and breast cancer cells grown in single culture. However, its effect in the tumor microenvironment remains unclear. This study aims to characterize cytokine profiles in media where TNBC cells and macrophages are grown in coculture with and without SFN treatment. We expect SFN to modify cytokine secretions in coculture media, suggesting SFN may disrupt vital cell-cell signaling needed for cancer progression. Methods TNBC cells (MDA-MB-231) were grown in Transwell plates with and without macrophages (THP-1 cells differentiated with PMA). Cell cultures (n = 3) were treated with either 15 μM SFN, DMSO (vehicle-control), or a non-treatment control. Cytokine levels were evaluated in media at 24 and 48 hours after treatment using BioPlex 2000 assay. Results Treatment with sulforaphane significantly reduced the levels of several targets in coculture including IL-1ra, IL-4, IL-5, IL-10, IL-12, IL-13, IL-15, IL-17, CCL2 (MCP-1), CCL11, CCL22, CCL26, CXCL12, IFN-y, G-CSF, GM-CSF, Eotaxin, and VEGF. Conversely, MIF was elevated following treatment. Effects were discovered at 24-hour and 48-hour time points. Conclusions We demonstrated that SFN altered the levels of numerous cellular signaling proteins in cancer cell-macrophage coculture, many of which are known to be involved with breast cancer progression. These results reveal mechanistic links underlying SFNs chemopreventive function and bolster SFNs potential as a treatment strategy for TNBC. Funding Sources Department of Nutrition and Food Science, CSU Chico; Graduate Studies, CSU Chico; CSUPERB: CSU Program for Education and Research in Biotechnology.

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