Abstract 374: Interleukin-19: A Novel Pro-Angiogenic and Anti-Inflammatory Adipokine

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Christine Vrakas ◽  
Sheri E Keleman ◽  
Rosario Scalia ◽  
Michael V Autieri
Keyword(s):  
Adipose Tissue ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Chow Diet ◽  
Vascular Cells ◽  
Regulatory Factor ◽  
Normal Chow ◽  
Gene Regulatory ◽  
Anti Inflammatory ◽  
Normal Chow Diet

Uncontrolled inflammation leads to many of the chronic diseases associated with obesity. Due to a lack of oxygen in the tissue, expanding adipose tissue becomes hypoxic and pro-inflammatory. Adipocytes release pro-angiogenic factors in an effort to restore blood flow to the tissue. Presently, little is known about the potential for endogenously expressed anti-inflammatory cytokines to attenuate inflammation and also provide pro-angiogenic effects. IL-19 is uniquely anti-inflammatory, pro-angiogenic and is both expressed by and targets various cells types. IL-19 expression in adipocytes and stromal vascular cells is increased in visceral compared to subcutaneous fat, and is also increased in visceral fat on high fat diet (HFD) compared to normal chow diet. There is no known mechanism to explain the role of IL-19 in adipose tissue expansion, and we hypothesized that IL-19 may have pro-angiogenic and anti-inflammatory properties in expanding adipose tissue. We have identified a gene regulatory factor, Interleukin Enhancer-Binding Factor 3 (ILF3) that is induced in adipocytes and stromal vascular cells by HFD and IL-19 treatment. We found that both IL-19 and VEGF induce ILF3 expression in cultured human endothelial cells (hECs). Proliferation is significantly reduced when ILF3 is knocked down using siRNA in hECs. Furthermore, when ILF3 is knocked down and hECs are stimulated with VEGF several angiogenic cytokines are also decreased. Through immunohistochemistry we found that ILF3 translocates from the nucleus to the cytoplasm in visceral fat of C57BL/6 mice fed a HFD, and remains in the nucleus when fed a normal chow diet. In summary IL-19 may be a unique HFD responsive adipokine functioning to reduce inflammation and increase angiogenesis in expanding adipose tissue. The angiogenic function of IL-19 may work through induction of the gene regulatory factor, ILF3.

scholarly journals Estrogens Protect against High-Fat Diet-Induced Insulin Resistance and Glucose Intolerance in Mice

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2109-2117 ◽  
Author(s):  
Elodie Riant ◽  
Aurélie Waget ◽  
Haude Cogo ◽  
Jean-François Arnal ◽  
Rémy Burcelin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Normal Chow ◽  
Visceral Adipose ◽  
Deficient Mice ◽  
Normal Chow Diet

Although corroborating data indicate that estrogens influence glucose metabolism through the activation of the estrogen receptor α (ERα), it has not been established whether this pathway could represent an effective therapeutic target to fight against metabolic disturbances induced by a high-fat diet (HFD). To this end, we first evaluated the influence of chronic 17β-estradiol (E2) administration in wild-type ovariectomized mice submitted to either a normal chow diet or a HFD. Whereas only a modest effect was observed in normal chow diet-fed mice, E2 administration exerted a protective effect against HFD-induced glucose intolerance, and this beneficial action was abolished in ERα-deficient mice. Furthermore, E2 treatment reduced HFD-induced insulin resistance by 50% during hyperinsulinemic euglycemic clamp studies and improved insulin signaling (Akt phosphorylation) in insulin-stimulated skeletal muscles. Unexpectedly, we found that E2 treatment enhanced cytokine (IL-6, TNF-α) and plasminogen activator inhibitor-1 mRNA expression induced by HFD in the liver and visceral adipose tissue. Interestingly, although the proinflammatory effect of E2 was abolished in visceral adipose tissue from chimeric mice grafted with bone marrow cells from ERα-deficient mice, the beneficial effect of the hormone on glucose tolerance was not altered, suggesting that the metabolic and inflammatory effects of estrogens can be dissociated. Eventually comparison of sham-operated with ovariectomized HFD-fed mice demonstrated that endogenous estrogens levels are sufficient to exert a full protective effect against insulin resistance and glucose intolerance. In conclusion, the regulation of the ERα pathway could represent an effective strategy to reduce the impact of high-fat diet-induced type 2 diabetes.

Metabolic in Vivo Labeling Highlights Differences of Metabolically Active Microbes from the Mucosal Gastrointestinal Microbiome between High-Fat and Normal Chow Diet

2017 ◽  
Vol 16 (4) ◽  
pp. 1593-1604 ◽  
Author(s):  
Andreas Oberbach ◽  
Sven-Bastiaan Haange ◽  
Nadine Schlichting ◽  
Marco Heinrich ◽  
Stefanie Lehmann ◽  
...  
Keyword(s):  
Chow Diet ◽  
High Fat ◽  
Gastrointestinal Microbiome ◽  
In Vivo Labeling ◽  
Normal Chow ◽  
Normal Chow Diet

scholarly journals Visceral obesity: A new risk factor for stone disease

2015 ◽  
Vol 9 (11-12) ◽  
pp. 795 ◽  
Author(s):  
Ilker Akarken ◽  
Hüseyin Tarhan ◽  
Rahmi Gökhan Ekin ◽  
Özgür Çakmak ◽  
Gökhan Koç ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Adipose Tissue ◽  
Kidney Stones ◽  
Visceral Fat ◽  
Subcutaneous Adipose Tissue ◽  
Subcutaneous Fat ◽  
Stone Disease ◽  
Flank Pain ◽  
Fat Tissue ◽  
Subcutaneous Adipose

Introduction: We examined the relationship between stone disease and the amount of visceral adipose tissue measured with unenhanced computed tomography (CT).Methods: We included 149 patients with complaints of flank pain and kidney stones detected by CT, from August 2012 to April 2013. In addition, as the control group we included 139 healthy individuals, with flank pain within the same time period, with no previous history of urological disease and no current kidney stones identified by CT. Patients were analyzed for age, gender, body mass index, amount of visceral and subcutaneous adipose tissue, and serum level of low-density lipoprotein and triglyceride.Results: There were no differences between groups in terms of gender and age (p = 0.27 and 0.06, respectively). Respective measurements for the stone and control groups for body mass index were 29.1 and 27.6 kg/m2; for visceral fat measurement 186.0 and 120.2 cm2; and for subcutaneous fat measurements 275.9 and 261.9 cm2 (p = 0.01; 0.01 and 0.36, respectively). Using multivariate analysis, the following factors were identified as increasing the risk of kidney stone formation: hyperlipidemia (p = 0.003), hypertension (p = 0.001), and ratio of visceral fat tissue to subcutaneous fat tissue (p = 0.01). Our study has its limitations, including its retrospective nature, its small sample size, possible selection bias, and missing data. The lack of stone composition data is another major limitation of our study.Conclusion: The ratio of visceral to subcutaneous adipose tissue, in addition to obesity, hyperlipidemia, and hypertension, was identified as an emerging factor in the formation of kidney stones.

scholarly journals Effects of Diet Induced Weight Reduction on Cartilage Pathology and Inflammatory Mediators in the Joint Tissues

2021 ◽  
Vol 8 ◽  
Author(s):  
Antonia RuJia Sun ◽  
Xiaoxin Wu ◽  
Ross Crawford ◽  
Hongxing Li ◽  
Lin Mei ◽  
...  
Keyword(s):  
Weight Loss ◽  
Inflammatory Cytokines ◽  
Cartilage Degeneration ◽  
Normal Diet ◽  
The Body ◽  
Chow Diet ◽  
Normal Chow ◽  
Obesogenic Diet ◽  
Dietary Switch ◽  
Normal Chow Diet

Obesogenic diets contribute to the pathology of osteoarthritis (OA) by altering systemic and local metabolic inflammation. Yet, it remains unclear how quickly and reproducibly the body responds to weight loss strategies and improve OA. In this study we tested whether switching obese diet to a normal chow diet can mitigate the detrimental effects of inflammatory pathways that contribute to OA pathology. Male C57BL/6 mice were first fed with obesogenic diet (high fat diet) and switched to normal chow diet (obese diet → normal diet) or continued obese diet or normal diet throughout the experiment. A mouse model of OA was induced by surgical destabilization of the medial meniscus (DMM) model into the knee joint. Outcome measures included changes in metabolic factors such as glucose, insulin, lipid, and serum cytokines levels. Inflammation in synovial biopsies was scored and inflammation was determined using FACs sorted macrophages. Cartilage degeneration was monitored using histopathology. Our results indicate, dietary switching (obese diet → normal diet) reduced body weight and restored metabolic parameters and showed less synovial tissue inflammation. Systemic blood concentrations of pro-inflammatory cytokines IL-1α, IL-6, IL-12p40, and IL-17 were decreased, and anti-inflammatory cytokines IL-4 and IL-13 were increased in dietary switch group compared to mice that were fed with obesogenic diet continuously. Although obese diet worsens the cartilage degeneration in DMM OA model, weight loss induced by dietary switch does not promote the histopathological changes of OA during this study period. Collectively, these data demonstrate that switching obesogenic diet to normal improved metabolic syndrome symptoms and can modulate both systemic and synovium inflammation levels.

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.

scholarly journals Cardiac mTOR rescues the detrimental effects of diet-induced obesity in the heart after ischemia-reperfusion

2015 ◽  
Vol 308 (12) ◽  
pp. H1530-H1539 ◽  
Author(s):  
Toshinori Aoyagi ◽  
Jason K. Higa ◽  
Hiroko Aoyagi ◽  
Naaiko Yorichika ◽  
Briana K. Shimada ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Chow Diet ◽  
In Vivo Models ◽  
Myocardial Scarring ◽  
Diet Induced Obesity ◽  
Normal Chow ◽  
Normal Chow Diet

Diet-induced obesity deteriorates the recovery of cardiac function after ischemia-reperfusion (I/R) injury. While mechanistic target of rapamycin (mTOR) is a key mediator of energy metabolism, the effects of cardiac mTOR in ischemic injury under metabolic syndrome remains undefined. Using cardiac-specific transgenic mice overexpressing mTOR (mTOR-Tg mice), we studied the effect of mTOR on cardiac function in both ex vivo and in vivo models of I/R injury in high-fat diet (HFD)-induced obese mice. mTOR-Tg and wild-type (WT) mice were fed a HFD (60% fat by calories) for 12 wk. Glucose intolerance and insulin resistance induced by the HFD were comparable between WT HFD-fed and mTOR-Tg HFD-fed mice. Functional recovery after I/R in the ex vivo Langendorff perfusion model was significantly lower in HFD-fed mice than normal chow diet-fed mice. mTOR-Tg mice demonstrated better cardiac function recovery and had less of the necrotic markers creatine kinase and lactate dehydrogenase in both feeding conditions. Additionally, mTOR overexpression suppressed expression of proinflammatory cytokines, including IL-6 and TNF-α, in both feeding conditions after I/R injury. In vivo I/R models showed that at 1 wk after I/R, HFD-fed mice exhibited worse cardiac function and larger myocardial scarring along myofibers compared with normal chow diet-fed mice. In both feeding conditions, mTOR overexpression preserved cardiac function and prevented myocardial scarring. These findings suggest that cardiac mTOR overexpression is sufficient to prevent the detrimental effects of diet-induced obesity on the heart after I/R, by reducing cardiac dysfunction and myocardial scarring.

Sexually dimorphic responses to fat loss after caloric restriction or surgical lipectomy

2007 ◽  
Vol 293 (1) ◽  
pp. E316-E326 ◽  
Author(s):  
Haifei Shi ◽  
April D. Strader ◽  
Stephen C. Woods ◽  
Randy J. Seeley
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Caloric Restriction ◽  
White Adipose Tissue ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Distribution Patterns ◽  
Male And Female ◽  
Fat Loss ◽  
Female Mice

White adipose tissue is the principal site for lipid accumulation. Males and females maintain distinctive white adipose tissue distribution patterns. Specifically, males tend to accumulate relatively more visceral fat, whereas females accumulate relatively more subcutaneous fat. The phenomenon of maintaining typical sex-specific fat distributions suggests sex-specific mechanisms that regulate energy balance and adiposity. We used two distinct approaches to reduce fat mass, caloric restriction (CR), and surgical fat removal (termed lipectomy) and assessed parameters involved in the regulation of energy balance. We found that male and female mice responded differentially to CR- and to lipectomy-induced fat loss. Females decreased energy expenditure during CR or after lipectomy. In contrast, males responded by eating more food during food return after CR or after lipectomy. Female CR mice conserved subcutaneous fat, whereas male CR mice lost adiposity equally in the subcutaneous and visceral depots. In addition, female mice had a reduced capability to restore visceral fat after fat loss. After CR, plasma leptin levels decreased in male but not in female mice. The failure to increase food intake after returning to ad libitum intake in females could be due to the relatively stable levels of leptin. In summary, we have found sexual dimorphisms in the response to fat loss that point to important underlying differences in the strategies by which male and female mice regulate body weight.

scholarly journals Unique Genetic and Histological Signatures of Mouse Pericardial Adipose Tissue

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1855
Author(s):  
A. Al-Dibouni ◽  
R. Gaspar ◽  
S. Ige ◽  
S. Boateng ◽  
F. R. Cagampang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Visceral Fat ◽  
Uncoupling Protein ◽  
Subcutaneous Fat ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Adipose Depot ◽  
Pericardial Adipose Tissue ◽  
Visceral Adipose ◽  
Adipose Tissue Depot

Obesity is a major risk factor for a plethora of metabolic disturbances including diabetes and cardiovascular disease. Accumulating evidence is showing that there is an adipose tissue depot-dependent relationship with obesity-induced metabolic dysfunction. While some adipose depots, such as subcutaneous fat, are generally metabolically innocuous, others such as visceral fat, are directly deleterious. A lesser known visceral adipose depot is the pericardial adipose tissue depot. We therefore set out to examine its transcriptional and morphological signature under chow and high-fat fed conditions, in comparison with other adipose depots, using a mouse model. Our results revealed that under chow conditions pericardial adipose tissue has uncoupling-protein 1 gene expression levels which are significantly higher than classical subcutaneous and visceral adipose depots. We also observed that under high-fat diet conditions, the pericardial adipose depot exhibits greatly upregulated transcript levels of inflammatory cytokines. Our results collectively indicate, for the first time, that the pericardial adipose tissue possesses a unique transcriptional and histological signature which has features of both a beige (brown fat-like) but also pro-inflammatory depot, such as visceral fat. This unique profile may be involved in metabolic dysfunction associated with obesity.

scholarly journals TIR-Domain-Containing Adaptor-Inducing Interferon-β (TRIF) Is Involved in Glucose Metabolism in Adipose Tissue through the Insulin/AKT Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Junling Yang ◽  
Ken-Ichiro Fukuchi
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Epididymal Adipose Tissue ◽  
Chow Diet ◽  
Low Grade ◽  
Interferon Β ◽  
Tlr Signaling ◽  
Normal Chow ◽  
Low Grade Inflammation

Obesity significantly increases the risk of developing type 2 diabetes mellitus and other metabolic diseases. Obesity is associated with chronic low-grade inflammation in white adipose tissues, which is thought to play an essential role in developing insulin resistance. Many lines of evidence indicate that toll-like receptors (TLRs) and their downstream signaling pathways are involved in development of chronic low-grade inflammation and insulin resistance, which are associated with obesity. Mice lacking molecules positively involved in the TLR signaling pathways are generally protected from high-fat diet-induced inflammation and insulin resistance. In this study, we have determined the effects of genetic deficiency of toll/interleukin-1 receptor-domain-containing adaptor-inducing interferon-β (TRIF) on food intake, bodyweight, glucose metabolism, adipose tissue macrophage polarization, and insulin signaling in normal chow diet-fed mice to investigate the role of the TRIF-dependent TLR signaling in adipose tissue metabolism and inflammation. TRIF deficiency (TRIF−/−) increased food intake and bodyweight. The significant increase in bodyweight in TRIF−/− mice was discernible as early as 24 weeks of age and sustained thereafter. TRIF−/− mice showed impaired glucose tolerance in glucose tolerance tests, but their insulin tolerance tests were similar to those in TRIF+/+ mice. Although no difference was found in the epididymal adipose mass between the two groups, the percentage of CD206+ M2 macrophages in epididymal adipose tissue decreased in TRIF−/− mice compared with those in TRIF+/+ mice. Furthermore, activation of epididymal adipose AKT in response to insulin stimulation was remarkably diminished in TRIF−/− mice compared with TRIF+/+ mice. Our results indicate that the TRIF-dependent TLR signaling contributes to maintaining insulin/AKT signaling and M2 macrophages in epididymal adipose tissue under a normal chow diet and provide new evidence that TLR4-targeted therapies for type 2 diabetes require caution.

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