scholarly journals Effects of Colchicine on Measures of Lipolysis in Adults With Obesity

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A9-A10
Author(s):  
Zahra Sarrafan-Chaharsoughi ◽  
Jordan A Levine ◽  
Tushar P Patel ◽  
Sheila M Brady ◽  
K Karthik Chivukula ◽  
...  

Abstract Background: Obesity-associated inflammation promotes adipose tissue (AT) dysfunction and contributes to the progression of type 2 diabetes and cardiovascular disease. Recent clinical studies have demonstrated that colchicine may improve metabolic and cardiovascular outcomes; however, colchicine’s effects on metabolic and inflammatory measures within AT remain unclear. Methods: The aim of this study was to examine if colchicine’s anti-inflammatory effects would improve measures of lipolysis and immune cell populations in subcutaneous AT (SAT). This is a secondary analysis of a double-blind, randomized, placebo-controlled pilot study in which 40 nondiabetic adults with obesity and metabolic syndrome (MetS) were randomized to colchicine 0.6mg or placebo twice daily for 3 months. Blood samples for insulin, glucose, and free fatty acids were collected in the fasted state and during a frequently-sampled intravenous glucose tolerance test. Noninsulin-suppressible (l0), insulin-suppressible (l2), and maximal (l0+l2) lipolysis rates were calculated by minimal model analysis. Body composition was determined by DXA. SAT immune cell populations were characterized by flow cytometry fluorescence-activated single cell sorting of the stromovascular fractions obtained after collagenase digestion of SAT samples obtained using a mini-liposuction technique pre- and post-intervention. Results: Data from 18 subjects in the colchicine group (Mean ± SD: age 48.4 ± 13.5 y; BMI 39.3 ± 6.3 kg/m2; sex: female 72.2%) and 18 subjects in the placebo group (age 44.7 ± 10.2 y; BMI 41.8 ± 8.2 kg/m2; sex: female 77.8%) were available for this study. Colchicine treatment significantly reduced l2 (p = 0.04) and l0+l2 (p = 0.04) versus placebo. These changes were significantly associated with reductions in systemic inflammation, including the changes in high-sensitivity C-reactive protein concentrations, white blood cell count, circulating monocyte and neutrophil populations, and the neutrophil-lymphocyte ratio (p’s < 0.015). Colchicine did not significantly alter SAT immune cell population distributions (p’s > 0.05). Conclusions: In adults with obesity and MetS, colchicine may improve insulin action at the level of AT. These improvements were positively associated with the suppression of systemic inflammation. However, no local AT inflammatory cell populations were significantly affected by colchicine use in our study, suggesting that colchicine’s systemic, rather than local, anti-inflammatory effects may be more consequential in ameliorating AT metabolic pathways in MetS. Further studies are warranted to elucidate the biological mechanisms underlying colchicine’s effects in AT, as these investigations could potentially shed light on treatments to improve metabolic outcomes in human obesity.

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Colleen Munoz ◽  
Jenna Apicella ◽  
Shlomit Radom‐Aizik ◽  
Carl Maresh ◽  
Faddia Haddad ◽  
...  

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 974
Author(s):  
Sang Seok Joo ◽  
Sang Jin Lee ◽  
Da Som Park ◽  
Dong Hyeon Kim ◽  
Bon-Hee Gu ◽  
...  

Owing to increasing global temperatures, heat stress is a major problem affecting dairy cows, and abnormal metabolic responses during heat stress likely influence dairy cow immunity. However, the mechanism of this crosstalk between metabolism and immunity during heat stress remains unclear. We used two representative dairy cow breeds, Holstein and Jersey, with distinct heat-resistance characteristics. To understand metabolic and immune responses to seasonal changes, normal environmental and high-heat environmental conditions, we assessed blood metabolites and immune cell populations. In biochemistry analysis from sera, we found that variety blood metabolites were decreased in both Holstein and Jersey cows by heat stress. We assessed changes in immune cell populations in peripheral blood mononuclear cells (PBMCs) using flow cytometry. There were breed-specific differences in immune-cell population changes. Heat stress only increased the proportion of B cells (CD4–CD21+) and heat stress tended to decrease the proportion of monocytes (CD11b+CD172a+) in Holstein cows. Our findings expand the understanding of the common and specific changes in metabolism and immune response of two dairy cow breeds under heat stress conditions.


KnE Medicine ◽  
2017 ◽  
Vol 1 (1) ◽  
pp. 173 ◽  
Author(s):  
Ilham Utama Surya ◽  
Achmad Kemal Harzif ◽  
Mila Maidarti ◽  
Gita Pratama ◽  
Budi Wiweko

<p>Implantation and growth of endometriosis was determined by immune cell. There were several immunologic cells that promoting implantation and cell proliferation such as macrophages, Natural killer, lymphocyte and monocyte. Infected endometrioma was associated in women with revised American Society for Reproductive Medicine (ASRM) stage III-IV. Neutrophil lymphocyte ratio (NLR) was a simple systemic inflammation response markers. The sensitivity and spesificity CA-125 in predicting endometrioma was very low but it had been used to monitor the progress of endometriosis. Therefore, measuring mean in leucocyte, NLR, PLR and CA-125 level in infected endometrioma was necessary. </p>


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A251-A251
Author(s):  
Dominic Pearce ◽  
Daniel Halligan ◽  
Patrick Fadden ◽  
Chassidy Hall ◽  
Amber Blackwell ◽  
...  

BackgroundExperimental therapies that target the immune system have expanded greatly in recent years due to the success of immune checkpoint inhibitory antibodies such as ipilimumab and pembrolizumab. Preclinical development of these novel immune-oncology drugs requires the availability of well characterized mouse models to evaluate therapeutic mode of action, efficacy, and safety. Syngeneic mouse tumor models provide robust systems in which to evaluate novel immune-oncology therapies. Efficacy in these models can be measured by tumor volume changes in subcutaneous implants or by impacts on survival for orthotopic implants. Mode of action can be assessed by identifying changes in the tumor microenvironment following dosing. Multiple analytical methods can be used to track changes in immune populations and activation status from flow cytometry to immunohistochemistry to gene expression analysis.MethodsWe endeavored to characterize the functional tumor microenvironment changes for two syngeneic models following treatment with anti-PD-1 and anti-CTLA-4 antibodies The syngeneic models used for the study were both colon adenocarcinomas, MC38 and CT26. Mice bearing subcutaneous tumors were dosed intraperitoneally with either vehicle alone, anti-CTLA-4, anti-PD-1, or a combination of the two immune checkpoint inhibitors on days 1, 4, and 8. Tumors were harvested on day 9 and assessed for gene expression by microarray analysis. The gene expression results were evaluated for the relationship between treatment regimen and tumor volume change by expression level association, functional set enrichment analysis, and immune cell population gene set variation analysis.ResultsFor each of the tumor models, >10,000 genes were found to be significantly differentially expressed. Functional set enrichment analysis showed notable changes in cell cycle and mitotic markers as well as immune response markers in MC38. In contrast, CT26 showed principally changes in immune response markers. Immune cell population set analysis revealed differential impacts on numerous immune cell populations between the models which correlate with therapy induced changes in tumor growth. These include expected changes in CD8+ T-cell populations for both models but also differential changes in other populations including CD56dim NK cells, eosinophils and B cells in MC38 and neutrophils in CT26. We also conducted a genomic analysis by whole exome sequencing. Both tumor models have relatively high tumor mutational burden; CT26 TMB = 377 MB and MC38 TMB = 69/MB. These data show the value of robust bioinformatics analysis of gene expression data sets to provide insights into the mode of action and model responses to investigational immune-oncology drugs.ConclusionsN/A


1960 ◽  
Vol XXXIII (II) ◽  
pp. 157-167
Author(s):  
T. Rodari ◽  
G. Specchia

ABSTRACT The double intravenous glucose tolerance test does not modify the assimilation coefficient in normal and thin diabetic subjects. On the contrary, in fat diabetic subjects the second coefficient of assimilation increases significantly, but not the first one. From these researches it is evident that the valuation of glucose assimilation by double venous hyperglycaemic test indicates the functional behaviour of the pancreas in different diabetic states. The interpretation of this behaviour of pancreatic islet response to the double venous hyperglycaemic test is discussed.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1981 ◽  
Author(s):  
Qiufen Mo ◽  
Aikun Fu ◽  
Lingli Deng ◽  
Minjie Zhao ◽  
Yang Li ◽  
...  

Glycerol monolaurate (GML) has potent antimicrobial and anti-inflammatory activities. The present study aimed to assess the dose-dependent antimicrobial-effects of GML on the gut microbiota, glucose and lipid metabolism and inflammatory response in C57BL/6 mice. Mice were fed on diets supplemented with GML at dose of 400, 800 and 1600 mg kg−1 for 4 months, respectively. Results showed that supplementation of GML, regardless of the dosages, induced modest body weight gain without affecting epididymal/brown fat pad, lipid profiles and glycemic markers. A high dose of GML (1600 mg kg−1) showed positive impacts on the anti-inflammatory TGF-β1 and IL-22. GML modulated the indigenous microbiota in a dose-dependent manner. It was found that 400 and 800 mg kg−1 GML improved the richness of Barnesiella, whereas a high dosage of GML (1600 mg kg−1) significantly increased the relative abundances of Clostridium XIVa, Oscillibacter and Parasutterella. The present work indicated that GML could upregulate the favorable microbial taxa without inducing systemic inflammation and dysfunction of glucose and lipid metabolism.


2020 ◽  
pp. 1-3
Author(s):  
Maximilian Jorczyk

<b>Introduction:</b> Macrolides have anti-inflammatory and immunomodulatory properties that give this class of antibiotics a role that differs from its classical use as an antibiotic, which opens new therapeutic possibilities. <b>Objective:</b> The aim of this study was to evaluate the anti-inflammatory effect of azithromycin in preventing mechanical ventilation (MV)-induced lung injury in very-low-birth-weight preterm neonates. <b>Methods:</b> This is a randomized, double-blind, placebo-controlled trial of preterm neonates who received invasive MV within 72 h of birth. Patients were randomized to receive intravenous azithromycin (at a dose of 10/mg/kg/day for 5 days) or placebo (0.9% saline) within 12 h of the start of MV. Two blood samples were collected (before and after intervention) for measurement of interleukins (ILs) and PCR for <i>Ureaplasma</i>. Patients were followed up throughout the hospital stay for the outcomes of death and bronchopulmonary dysplasia defined as need for oxygen for a period of ≥28 days of life (registered at ClinicalTrials.gov, No. NCT03485703). <b>Results:</b> Forty patients were analyzed in the azithromycin group and 40 in the placebo group. Five days after the last dose, serum IL-2 and IL-8 levels dropped significantly in the azithromycin group. There was a significant reduction in the incidence of death and O<sub>2</sub> dependency at 28 days/death in azithromycin-treated patients regardless of the detection of <i>Ureaplasma</i> in blood. <b>Conclusions:</b> Azithromycin has anti-inflammatory effects, with a decrease in cytokines after 5 days of use and a reduction in death and O<sub>2</sub> dependency at 28 days/death in mechanically ventilated preterm neonates.


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