scholarly journals Pathogenetic Interplay Between IL-6 and Tryptophan Metabolism in an Experimental Model of Obesity

2021 ◽  
Vol 12 ◽  
Author(s):  
Giada Mondanelli ◽  
Elisa Albini ◽  
Elena Orecchini ◽  
Maria Teresa Pallotta ◽  
Maria Laura Belladonna ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Immune Escape ◽  
Stromal Vascular Fraction ◽  
Kynurenine Pathway ◽  
Standard Diet ◽  
Low Grade ◽  
Tumor Immune Escape ◽  
Insulin Resistant ◽  
Ido1 Expression ◽  
Low Grade Inflammation

Obesity is a metabolic disease characterized by a state of chronic, low-grade inflammation and dominated by pro-inflammatory cytokines such as IL-6. Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that catalyzes the first step in the kynurenine pathway by transforming l-tryptophan (Trp) into l-kynurenine (Kyn), a metabolite endowed with anti-inflammatory and immunoregulatory effects. In dendritic cells, IL-6 induces IDO1 proteasomal degradation and shuts down IDO1-mediated immunosuppressive effects. In tumor cells, IL-6 upregulates IDO1 expression and favors tumor immune escape mechanisms. To investigate the role of IDO1 and its possible relationship with IL-6 in obesity, we induced the disease by feeding mice with a high fat diet (HFD). Mice on a standard diet were used as control. Experimental obesity was associated with high IDO1 expression and Kyn levels in the stromal vascular fraction of visceral white adipose tissue (SVF WAT). IDO1-deficient mice on HFD gained less weight and were less insulin resistant as compared to wild type counterparts. Administration of tocilizumab (TCZ), an IL-6 receptor (IL-6R) antagonist, to mice on HFD significantly reduced weight gain, controlled adipose tissue hypertrophy, increased insulin sensitivity, and induced a better glucose tolerance. TCZ also induced a dramatic inhibition of IDO1 expression and Kyn production in the SVF WAT. Thus our data indicated that the IL-6/IDO1 axis may play a pathogenetic role in a chronic, low-grade inflammation condition, and, perhaps most importantly, IL-6R blockade may be considered a valid option for obesity treatment.

scholarly journals A Distinct Cytokine Profile and Stromal Vascular Fraction Metabolic Status without Significant Changes in the Lipid Composition Characterizes Lipedema

2021 ◽  
Vol 22 (7) ◽  
pp. 3313
Author(s):  
Stefan Wolf ◽  
Jeremy W. Deuel ◽  
Maija Hollmén ◽  
Gunther Felmerer ◽  
Bong-Sung Kim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Metabolic Activity ◽  
Lipid Composition ◽  
Subcutaneous Fat ◽  
Stromal Vascular Fraction ◽  
Cytokine Profile ◽  
Metabolic Phenotype ◽  
Low Grade ◽  
And Control ◽  
Low Grade Inflammation

Lipedema is an adipose tissue disorder characterized by the disproportionate increase of subcutaneous fat tissue in the lower and/or upper extremities. The underlying pathomechanism remains unclear and no molecular biomarkers to distinguish the disease exist, leading to a large number of undiagnosed and misdiagnosed patients. To unravel the distinct molecular characteristic of lipedema we performed lipidomic analysis of the adipose tissue and serum of lipedema versus anatomically- and body mass index (BMI)-matched control patients. Both tissue groups showed no significant changes regarding lipid composition. As hyperplastic adipose tissue represents low-grade inflammation, the potential systemic effects on circulating cytokines were evaluated in lipedema and control patients using the Multiplex immunoassay system. Interestingly, increased systemic levels of interleukin 11 (p = 0.03), interleukin 28A (p = 0.04) and interleukin 29 (p = 0.04) were observed. As cytokines can influence metabolic activity, the metabolic phenotype of the stromal vascular fraction was examined, revealing significantly increased mitochondrial respiration in lipedema. In conclusion, despite sharing a comparable lipid profile with healthy adipose tissue, lipedema is characterized by a distinct systemic cytokine profile and metabolic activity of the stromal vascular fraction.

Adipose tissue inflammation and insulin resistance: all obese humans are not created equal

2010 ◽  
Vol 430 (2) ◽  
pp. e1-e4 ◽  
Author(s):  
Marie-Soleil Gauthier ◽  
Neil B. Ruderman
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Obese Individual ◽  
Low Grade ◽  
Key Factors ◽  
Insulin Resistant ◽  
The Metabolic Syndrome ◽  
Biochemical Journal ◽  
Visceral Adipose ◽  
Low Grade Inflammation

In recent years, it has become widely accepted that obesity is characterized by a chronic low-grade inflammation of adipose tissue that predisposes affected individuals to insulin resistance, Type 2 diabetes and other disorders associated with the metabolic syndrome. On the other hand, a subset of obese individuals appears to be protected against insulin resistance and the disorders to which it predisposes. The comparison between such insulin-sensitive and insulin-resistant obese individuals offers a unique opportunity to identify key factors that either contribute to or prevent the development of insulin resistance in humans, without the confounding effect of a major difference in fat mass. In the previous issue of the Biochemical Journal, Barbarroja et al. reported that insulin-sensitive obese individuals show less inflammation in their visceral adipose tissue than a group of insulin-resistant subjects matched for BMI (body mass index). This finding reinforces the concept that inflammation in adipose tissue may be a cause of insulin resistance in most obese individuals, although it does not prove it. Further studies will be required for this purpose, as well as to identify the pathogenetic factors that determine whether or not adipose tissue of an obese individual becomes inflamed.

The Role of Epicardial Adipose Tissue Lymphocytes in Low-Grade Inflammation and Coronary Artery Disease

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 469-P
Author(s):  
MILOS MRAZ ◽  
ANNA CINKAJZLOVA ◽  
ZDENA LACINOVÁ ◽  
JANA KLOUCKOVA ◽  
HELENA KRATOCHVILOVA ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Epicardial Adipose Tissue ◽  
Low Grade ◽  
Artery Disease ◽  
Low Grade Inflammation

scholarly journals Adipose tissue inflammation and metabolic dysfunction: a clinical perspective

2013 ◽  
Vol 15 (1) ◽  
Author(s):  
Charmaine S. Tam ◽  
Leanne M. Redman
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Low Grade ◽  
Metabolic Dysfunction ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Proinflammatory Mediators ◽  
Low Grade Inflammation

AbstractObesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).

Tryptophan metabolism activation by indoleamine 2,3-dioxygenase in adipose tissue of obese women: an attempt to maintain immune homeostasis and vascular tone

2012 ◽  
Vol 303 (2) ◽  
pp. R135-R143 ◽  
Author(s):  
Isabelle Wolowczuk ◽  
Benjamin Hennart ◽  
Audrey Leloire ◽  
Alban Bessede ◽  
Marion Soichot ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
T Cell ◽  
White Adipose Tissue ◽  
Vascular Tone ◽  
T Cell Subsets ◽  
Low Grade ◽  
Adipose Tissues ◽  
Indoleamine 2,3 Dioxygenase ◽  
Arterial Blood ◽  
Ido1 Expression

Human obesity is characterized by chronic low-grade inflammation in white adipose tissue and is often associated with hypertension. The potential induction of indoleamine 2,3-dioxygenase-1 (IDO1), the rate-limiting enzyme in tryptophan/kynurenine degradation pathway, by proinflammatory cytokines, could be associated with these disorders but has remained unexplored in obesity. Using immunohistochemistry, we detected IDO1 expression in white adipose tissue of obese patients, and we focused on its contribution in the regulation of vascular tone and on its immunoregulatory effects. Concentrations of tryptophan and kynurenine were measured in sera of 36 obese and 15 lean women. The expression of IDO1 in corresponding omental and subcutaneous adipose tissues and liver was evaluated. Proinflammatory markers and T-cell subsets were analyzed in adipose tissue via the expression of CD14, IL-18, CD68, TNFα, CD3ε, FOXP3 [a regulatory T-cell (Treg) marker] and RORC (a Th17 marker). In obese subjects, the ratio of kynurenine to tryptophan, which reflects IDO1 activation, is higher than in lean subjects. Furthermore, IDO1 expression in both adipose tissues and liver is increased and is inversely correlated with arterial blood pressure. Inflammation is associated with a T-cell infiltration in obese adipose tissue, with predominance of Th17 in the omental compartment and of Treg in the subcutaneous depot. The Th17/Treg balance is decreased in subcutaneous fat and correlates with IDO1 activation. In contrast, in the omental compartment, despite IDO1 activation, the Th17/Treg balance control is impaired. Taken together, our results suggest that IDO1 activation represents a local compensatory mechanism to limit obesity-induced inflammation and hypertension.

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>

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