Adipose Tissue Is a Major Source of Interleukin-1 Receptor Antagonist

Juge-Aubry, Cristiana E.; Somm, Emmanuel; Giusti, Vittorio; Pernin, Agnès; Chicheportiche, Rachel; Verdumo, Chantal; Rohner‐Jeanrenaud, Françoise; Burger, Danielle; Dayer, Jean‐Michel; Meier, Christoph A.

doi:10.2337/diabetes.52.5.1104

Cited by 262 publications

(223 citation statements)

References 30 publications

(18 reference statements)

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“…PPARγ is stimulated during adipocyte differentiation, and is also involved in the resolution of inflammation in many other cell types, in which it downregulates levels of inflammatory proteins, such as COX-2 and IL-1β. In fact, the expression pattern of IL-33 was more similar to that of IL-1 receptor antagonist, the natural inhibitor of IL-1β, which is also expressed in non-inflammatory bone [41] and in adipocytes (our unpublished data and [42]). It will be interesting to examine whether the expression of IL-33, like that of IL-1Ra, is also controlled by PPARα [43,44] and PPARβ/δ [45].…”

Section: Discussionmentioning

confidence: 58%

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

et al. 2011

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1 IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodelingsuggested that expression of IL-33, in contrast to that of IL-1β, is not repressed by PPARγ, likely explaining why IL-33, but not IL-1β, is expressed in adipocytes. The IL-33 receptor ST2L is not constitutively expressed in human bone marrow stromal cells, osteoblasts or CD14-positive monocytes, and IL-33 has no effect on these cells. In addition, although ST2L mRNA is induced by TNF-α and IL-1β in bone marrow stromal cells, IL-33 has the same effects as TNF-α and IL-1β, and, therefore, the biological activity of IL-33 may be redundant in this system. In agreement with this hypothesis, MC3T3-E1 osteoblast-like cells constitutively express ST2L mRNA, and in these cells IL-33 and TNF-α/IL-1β similarly decrease osteocalcin RNA levels in these cells. In conclusion, our results suggest that IL-33 has no direct effects on normal bone remodeling.

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Section: Discussionmentioning

confidence: 58%

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

et al. 2011

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“…Human and rodent WAT is a major source of IL1RN [43,44]. Il1rn −/− mice, in which excess IL1 signalling may be induced, show a lean phenotype [45].…”

Section: Discussionmentioning

confidence: 99%

C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet

et al. 2007

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Aims/hypothesis Inflammation is associated with obesity and has been implicated in the development of diabetes and atherosclerosis. During gram-negative bacterial infection, lipopolysaccharide causes an inflammatory reaction via toll-like receptor 4 (TLR4), which has an essential function in the induction of innate and adaptative immunity. Our aim was to determine what role TLR4 plays in the development of metabolic phenotypes during high-fat feeding. Materials and methods We evaluated metabolic consequences of a high-fat diet in TLR4 mutant mice (C3H/HeJ) and their respective controls. Results TLR4 inactivation reduced food intake without significant modification of body weight, but with higher epididymal adipose tissue mass and adipocyte hypertrophy. It also attenuated the inflammatory response and increased glucose transport and the expression levels of adiponectin and lipogenic markers in white adipose tissue. In addition, TLR4 inactivation blunted insulin resistance induced by lipopolysaccharide in differentiated adipocytes. Increased feeding efficiency in TLR4 mutant mice was associated with lower mass and lower expression of uncoupling protein 1 gene in brown adipose tissue. Finally, TLR4 inactivation slowed the development of hepatic steatosis, reducing the liver triacylglycerol content and also expression levels of lipogenic and fibrosis markers. Conclusions/interpretation TLR4 influences white adipose tissue inflammation and insulin sensitivity, as well as liver fat storage, and is important in the regulation of metabolic phenotype during a fat-enriched diet.

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“…30 White adipose tissue (WAT) is a major source of leptin and IL-1Ra in humans and rodents and the expression of these cytokines is markedly upregulated in obese WAT. 21,31 The macrophage content of WAT is significantly increased in obesity, mediated partly through increased infiltration of circulating macrophages, and this is thought to be a mechanism contributing to elevated cytokine levels. 32 Supporting this, leptin produced by adipocytes stimulates IL-1Ra production by monocytes, through binding to leptin receptors expressed on these cells.…”

Section: Discussionmentioning

confidence: 99%

Stress-induced cytokine responses and central adiposity in young women

et al. 2007

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Background: Evidence suggests that people who are more responsive to psychological stress are at an increased risk of developing obesity. However, the biological mechanisms underlying this phenomenon are poorly understood. The cytokines leptin, interleukin-1 receptor antagonist (IL-1Ra) and interleukin-6 (IL-6) play a key role in fat metabolism and abnormal circulating levels of these proteins have been reported in obese people and in individuals subject to stress. Objective: This study investigated whether cytokine responses to acute mental stress are associated with adiposity in healthy young women. Design and Subjects: A laboratory study of 67 women, aged 18-25 years, recruited from University College London. Measurements: Height, weight and waist circumference were measured and body fat mass was estimated by bioelectrical impedance body composition analysis. Laboratory mental stress testing was carried out and blood pressure and heart rate were recorded at baseline, during two moderately challenging tasks (Stroop and speech) and during recovery 40-45 min post-stress. Blood samples taken at baseline, immediately post-stress and 45 min post-stress, were used for assessment of circulating cytokines. Saliva samples taken throughout the session were assessed for cortisol. Results: Women who had larger cytokine responses to stress were more abdominally obese than women with smaller cytokine stress responses. Specifically, there was a positive correlation between waist circumference and stress-induced increases in plasma levels of leptin (r ¼ 0.35, Po0.05) and IL-1Ra responses (r ¼ 0.29, Po0.05). There was also a significant positive correlation between prolonged diastolic blood pressure responses to stress and measures of total and abdominal obesity (r ¼ 0.28-0.33, Po0.05). Conclusion: Increased cytokine production could be a mechanism linking stress and abdominal obesity.

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Adipose Tissue Is a Major Source of Interleukin-1 Receptor Antagonist

Cited by 262 publications

References 30 publications

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet

Stress-induced cytokine responses and central adiposity in young women

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