Abstract 5466: In Vivo Molecular Imaging Revealed Chronic Inflammation and Increased Adhesion Molecules in Obese Adipose Tissue in Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Satoshi Nishimura ◽  
Mika Nagasaki ◽  
Ichiro Manabe ◽  
Kinya Seo ◽  
Takashi Kadowaki ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Chronic Inflammation ◽  
Adhesion Molecules ◽  
Visceral Adipose Tissue ◽  
Ex Vivo ◽  
Subcutaneous Fat ◽  
Therapeutic Interventions ◽  
Imaging Method ◽  
Visceral Adipose

Metabolic syndrome is a major risk factor of cardiovascular events, and obese visceral adipose tissue remodeling and malfunctioning based on chronic inflammation plays a central role. To assess dynamic multi-cellular interplay, a novel ex vivo (a–c) and in vivo (d–f) adipose tissue imaging method was developed. We found close spatial and temporal interrelationships between angiogenesis and adipogenesis, and both were augmented in obese adipose (c,arrow). In addition, we found increased leukocyte-platelet-endothelial cell interactions in the micro-circulation of obese visceral adipose that were indicative of activation of the leukocyte adhesion cascade, a hallmark of inflammation (e,f). Both macrophages and endothelial cells showed increased adhesion molecules including ICAM-1 and Selectin families, and P-selectin positive platelets were increased locally in obese adipose. Up-regulated expression of adhesion molecules on multiple cell types suggests their increased interactions contribute to local activation of inflammatory processes within visceral obese adipose tissue. Interestingly, the heightened leukocyte-platelet-endothelial interactions were not observed in obese subcutaneous fat pads. Our results demonstrated the power of our imaging technique to analyze complex inflammatory cellular interplays in vivo and to evaluate new therapeutic interventions against them. Results also indicate that visceral adipose tissue obesity is an inflammatory disease.

scholarly journals Multinucleated giant cells in adipose tissue are specialized in adipocyte degradation

2020 ◽  
Author(s):  
Ada Admin ◽  
Julia Braune ◽  
Andreas Lindhorst ◽  
Janine Fröba ◽  
Constance Hobusch ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Ex Vivo ◽  
Giant Cells ◽  
Low Grade ◽  
Adipose Tissue Macrophages ◽  
Visceral Adipose ◽  
Low Grade Inflammation

Obesity is associated with a chronic low-grade inflammation in visceral adipose tissue (AT) characterized by an increasing number of adipose tissue macrophages (ATMs) and linked to type 2 diabetes. AT inflammation is histologically indicated by the formation of so-called crown-like structures (CLS), as accumulation of ATMs around dying adipocytes, and the occurrence of multi-nucleated giant cells (MGCs). However to date, the function of MGCs in obesity is unknown. Hence, the aim of this study was to characterize MGCs in AT and unravel the function of these cells. <p>We demonstrate that MGCs occur in obese patients and after 24 weeks of high fat diet (HFD) in mice, accompanying signs of AT inflammation and then represent ~3% of ATMs in mice. Mechanistically, we found evidence that adipocyte death triggers MGC formation. Most importantly, MGCs in obese AT have a higher capacity to phagocytose oversized particles, such as adipocytes, as shown by live-imaging of AT, 45 µm bead uptake <i>ex vivo</i> and a higher lipid content <i>in vivo</i>. Finally, we show that IL-4 treatment is sufficient to increase the number of MGCs in AT, whereas other factors maybe more important for endogenous MGC formation <i>in vivo</i>.</p>

Abstract 5822: Atherosclerotic Plaque Inflammation Synchronize With Inflammatory Activity OF Visceral Fat

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Eung Ju Kim ◽  
Hong Seog Seo ◽  
Sungeun Kim ◽  
Jin Oh Na ◽  
Jae Hyoung Park ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Atherosclerotic Plaque ◽  
Visceral Adipose Tissue ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Fdg Uptake ◽  
Coronary Syndrome ◽  
Significant Difference ◽  
Plaque Inflammation ◽  
Visceral Adipose

Background: Visceral adipose tissue is thought to confer increased cardiovascular risk through leukocyte infiltration and increased adipose macrophage activity. Previous positron emission tomography (PET) studies using fluorodeoxyglucose (FDG) demonstrated that increased FDG uptake could reflect the severity of inflammation in atherosclerotic plaque. We hypothesized that active atherosclerotic change in the major arteries would accompany increased inflammation within visceral fat and it could be detected in humans using combined FDG PET/computed tomography (CT). Methods: We observed 44 consecutive subjects with cardiovascular disease. For all of them, an one-hour PET/CT (from brain to foot) was performed after injection of FDG (370–555 MBq). FDG uptake in the aorta or its major branches was evaluated visually and semiquantitatively. Maximal standard uptake values (SUV) of the highest regions of interest were calculated in the subcutaneous fat and visceral fat area, separately. Results: Significant FDG uptake in the arterial wall was noted in 21 patients (plaque positive; PP group), all of whom have experienced acute cardiovascular events (acute coronary syndrome or ischemic stroke) within a week. The other 23 patients (plaque negative; PN group) had chronic stable angina or asymptomatic carotid stenosis. Visceral fat SUV was significantly higher as compared to subcutaneous fat SUV (0.49± 0.15 vs. 0.15± 0.05, p< 0.001) in PP group, whereas there was no significant difference in PN group (0.18± 0.07 vs. 0.16± 0.03, p= 0.622). When we compared two groups, PP group showed higher visceral fat SUV than PN group (p< 0.001). In terms of subcutaneous fat SUV, the results were similar in two groups (p= 0.773). Conclusions: We demonstrated that atherosclerotic plaque inflammation was associated with increased inflammation within visceral fat. Our results need to be confirmed by comparison with histologic or other imaging findings. Further evaluation to determine whether metabolic activity of visceral adipose tissue is a marker or mediator of vascular inflammation is also needed.

Abstract 14315: New Insights Into the Mechanisms of Sepsis: The Role of Proprotein Convertase Subtilisin/kexin Type 9 as a Key Regulator of Pathogen Toxin Clearance

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Elena Topchiy ◽  
Yingjin Wang ◽  
John Boyd ◽  
Keith R Walley
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Ex Vivo ◽  
Fluorescent Microscopy ◽  
Hepatic Uptake ◽  
Cardiovascular Complications ◽  
Proprotein Convertase ◽  
Bacterial Endotoxins ◽  
Visceral Adipose

Background: To prevent severe inflammation during infection, the patient must quickly clear bacterial endotoxins from the circulation before they accumulate and are able to interact with immune cells and vascular endothelium, and induce inflammatory organ failure. Bacterial endotoxins are carried within lipoprotein particles. Thus, one mechanism of action for sepsis treatments could be acceleration of lipoprotein clearance by adipocytes and hepatocytes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases the rate of lipoprotein clearance. We have recently reported that reduced function of PCSK9 improves outcome and prevents cardiovascular complications associated with sepsis. Hypothesis: PCSK9 inhibits LDL associated LPS clearance through hepatic LDLR and VLDL associated LPS clearance through adipose VLDLR. Methods and Results: Using siRNA against the LDLR in HepG2 hepatocytes decreased uptake of fluorescently labeled LPS (fLPS) after 48 hours by 1.50±0.10 fold (n=3, p<0.05). Addition of recombinant PCSK9 in the absence of LDLR did not alter uptake of LPS. We confirmed that hepatic uptake of LPS is exclusively via the LDLR by fluorescent microscopy of ex vivo LPS treated primary hepatocytes isolated from LDLR -/- mice. To address the importance of the LDLR upon clearance of LPS from plasma, we injected fLPS into the portal vein of LDLR-/-, PCSK9-/- and wild type mice (WT). Compared to WT, LDLR-/- mice had 36±13% (n=9, p<0.001) increase in plasma LPS after 1 hour, whereas PCSK9-/- show a significant decrease (28±4%, n=9, p<0.001) in plasma LPS. LDLR-/-, but not PCSK9-/- mice showed 46±7% decrease (n=10, p<0.05) in hepatic uptake. On the other hand, compared to the WT PCSK9-/- mice had 200±35% (n=8, p<0.001) increase in LPS uptake by visceral adipose tissue whereas LDLR-/- had no effect compared to WT mice. To further investigate LPS uptake by adipose tissue we injected flLPS into the tail vein of VLDLR-/- and WT mice. VLDLR-/- mice had 33±6% (n=10, p<0.001) decrease in visceral adipose tissue uptake, with no significant change in hepatic uptake. Conclusions: Expression of hepatic LDLR and adipose VLDLR is mainly regulated by PCSK9 and both play important role in clearing LPS from circulation.

scholarly journals Obesity and COVID-19: The role of visceral adipose tissue

2020 ◽  
Author(s):  
Antonia Petersen ◽  
Keno Bressem ◽  
Jakob Albrecht ◽  
Hans-Martin Thiess ◽  
Janis Vahldiek ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Subcutaneous Fat ◽  
Abdominal Circumference ◽  
Health Crisis ◽  
Increased Risk ◽  
Upper Abdominal ◽  
Visceral Adipose ◽  
Icu Treatment

INTRODUCTION: During the unprecedented health crisis of the COVID-19 pandemic it was suggested that obesity might aggravate severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). Therefore, this study aims to investigate the association between Compute Tomography (CT)-based measurements of visceral and subcutaneous fat as measures of obesity and COVID-19 severity. METHODS: 30 patients with laboratory-confirmed COVID-19 and a mean age of 65.59 plus/minus 13.06 years from a level one medical center in Berlin, Germany, were retrospectively analyzed and included in the present analysis. SARS-CoV-2 was confirmed by polymerase chain reaction from throat swaps or deep nasal swabs on the day of admission. Severe clinical courses of COVID-19 were defined by hospitalization in intensive care unit (ICU) and invasive mechanical ventilation. All patients received low-dose chest CT-based fat measurements at the level of the first lumbar vertebra. RESULTS: An increase in visceral fat area (VFA) by one square decimeter was associated with a 22.53-fold increased risk for ICU treatment and a 16.11-fold increased risk for mechanical ventilation (adjusted for age and sex). For upper abdominal circumference, each additional centimeter of circumference showed a 1.13-fold increased risk for ICU treatment and a 1.25-fold increased risk for mechanical ventilation. There was no significant correlation of subcutaneous fat area (SFA) or body mass index (BMI) with severe clinical courses of COVID-19. CONCLUSIONS: Our results suggest that visceral adipose tissue and upper abdominal circumference specifically increasing the risk of COVID-19 severity. CT-based quantification of visceral adipose tissue and upper abdominal circumference in routinely acquired chest CTs may therefore be a simple tool for risk assessment in SARS-CoV-2-patients.

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