Adipose tissue expression of interleukin-18 mRNA is elevated in subjects with metabolic syndrome and independently associated with fasting glucose

Weiss, Thomas W.; Arnesen, Harald; Trøseid, Marius; Kaun, Christoph; Hjerkinn, Elsa M.; Huber, Kurt; Wojta, Johann; Seljeflot, Ingebjørg

doi:10.1007/s00508-011-0028-6

Cited by 17 publications

(16 citation statements)

References 19 publications

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“…The importance of IL-18 in MetS was also underlined in a review by Trøseid et al [30]. It was also recently shown increased IL-18 mRNA expression in adipose tissue from MetS subjects compared to non-MetS individuals [31]. We could further demonstrate that the influence of the +183 A/G polymorphism was especially apparent in the T2DM and Mets groups, suggesting a beneficial influence of the G-allele in these patients.…”

Section: Discussionsupporting

confidence: 72%

Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an Observational Study

Opstad

Pettersen

Arnesen

et al. 2011

Cardiovasc Diabetol

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BackgroundIncreased IL-18 serum levels have been associated with diabetes type 2, metabolic syndrome and the severity of atherosclerosis. The present study investigated the presence and influence of IL-18 genetic variants on gene- and protein expression in stable coronary artery disease (CAD) patients.MethodsThe +183 A/G (rs 5744292), -137 G/C (rs 187238) and -607 C/A (rs 1946518) polymorphisms were determined in 1001 patients with angiographically verified stable CAD, and in 204 healthy controls. IL-18 gene-expression was measured in circulating leukocytes in 240 randomly selected patients. Circulating IL-18 and IL-18 binding protein levels were measured immunologically in all patients.ResultsThe +183 G-allele associated significantly with lower serum levels of IL-18 (p = 0.002, adjusted for age, glucose, body mass index and gender) and a 1.13- fold higher IL-18 gene-expression (p = 0.010). No influence was observed for the -137 G/C and -607 C/A polymorphisms. The IL-18 binding protein levels were not influenced by IL-18 genotypes. IL-18 levels were significantly higher in men as compared to women, and in patients with diabetes type 2 and metabolic syndrome compared to those without (p ≤ 0.001, all). The reduction in IL-18 levels according to the +183 G-allele was 3-4 fold more pronounced in diabetes and metabolic syndrome as compared to unaffected patients.Finally, the +183 AA genotype was more frequent in patients with hypertension (p = 0.042, adjusted for age, body mass index and gender).ConclusionThe reduction in serum IL-18 levels across increasing numbers of +183G-alleles was especially apparent in patient with diabetes type 2 and metabolic syndrome, suggesting a beneficial GG genotype in relation to cardiovascular outcome in these patients.Clinical Trial Registration NumberClinicalTrials.gov: NCT00222261

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Section: Discussionsupporting

confidence: 72%

Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an Observational Study

Opstad

Pettersen

Arnesen

et al. 2011

Cardiovasc Diabetol

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“…We observed a significant decrease in leptin levels after euthyroidism was achieved. Study by Yildiz BO et al demonstrated a decrease in leptin levels without a change in fat mass after euthyroidvarious adipokines and inflammatory cytokines involved in atherogenesis, atherothrombosis, and arterial plaque rupture [2,28,29]. Adipocytes express TSH receptors, and VAT proliferation can take place based on TSH expression in visceral and adipose tissue [30].…”

Section: Discussionmentioning

confidence: 95%

Changes in the before and after thyroxine treatment levels of adipose tissue, leptin, and resistin in subclinical hypothyroid patients

Akbaba

Berker

Işık

et al. 2015

Wien Klin Wochenschr

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Initially, high sensitivity C-reactive protein, carotid artery intima-media thickness (mm), leptin, and resistin levels were significantly higher in the SH group compared to the controls, while the other parameters were similar. While no correlation was observed between TSH levels and adipokines, a positive correlation was detected between waist circumference and leptin levels (r = 0.549, p < 0.01). Visceral adipose tissue was positively correlated to age, waist circumference, and leptin levels, but negatively correlated to free thyroxin (T4) levels (r = 0.419, p = 0.009; r = 0.794, p < 0.01; r = 0.515, p < 0.01 and r = - 0.416, p = 0.009, respectively). A significant decrease was observed in VAT volume, leptin, and resistin levels of SH patients following levothyroxine treatment. Conclusion The reduced VAT volume, leptin, and resistin levels in SH patients following treatment may support the idea that TSH affects adipose tissue functions.

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“…Such a finding is consistent with the increased adipocytokine release from adipose tissue in obesity (Fain, 2006). Accordingly, fat-resident monocyte/macrophage lineage cells are major sources of circulating IL-18 (Fain, 2006), adipocytes from obese humans secrete 3-fold more IL-18 than those from lean donors (Skurk et al, 2005), and subcutaneous adipose tissue expression of IL-18 is elevated in obesity and metabolic syndrome disorders (Bruun et al, 2007; Leick et al, 2007; Membrez et al, 2009; Weiss et al, 2011). Consistent with a signal of metabolic state, circulating IL-18 levels are increased by hyperglycemia or a high-fat meal (Esposito et al, 2002a; Esposito et al, 2003), and intermittent glucose exposure increases the secretion of IL-18 by adipocytes (Sun et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-18 null mutation increases weight and food intake and reduces energy expenditure and lipid substrate utilization in high-fat diet fed mice

Zorrilla

Conti

2014

Brain, Behavior, and Immunity

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Objective The proinflammatory cytokine interleukin-18 (IL-18) putatively modulates food intake and energy metabolism, but the effects of IL-18 in high-fat diet fed animals are unknown. Whether IL-18 alters basal metabolic rate or metabolic processes of living is unknown. Here, we tested the hypothesis that IL-18 modulates weight gain, energy intake, whole-body energy expenditure, and utilization of lipid as a fuel substrate in high-fat diet fed mice. Methods Food intake, whole-body metabolism, and motor activity of IL-18 knockout mice were compared to those of wildtype littermates; anorectic effects of intracerebroventricular IL-18 administration were compared between IL-18 receptor knockout, IL-18/IL-18R knockout and wildtype mice. Results Chow-reared IL-18 knockout mice were overweight at 6 months of age and then gained excess weight on both low-fat and high-fat diets, ate more high-fat diet, and showed reduced whole-body energy expenditure and increased respiratory exchange ratios. Reductions in energy expenditure of IL-18 knockout mice were seen across fasting vs. feeding conditions, low- vs. high-fat diets, high vs. low levels of physical activity and times of day, suggesting actions on basal metabolic rate. The circadian amplitude of energy expenditure, but not respiratory exchange ratio, food intake, or motor activity, also was blunted in IL-18 knockout mice. Central IL-18 administration reduced high-fat diet intake in wildtype mice, but not in mice lacking the IL-18 receptor. Conclusion The loss-of-function results support the hypothesis that endogenous IL-18 suppresses appetite and promote energy expenditure and lipid fuel substrate utilization not only during sickness, but also in healthy adults consuming high-fat diets.

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Adipose tissue expression of interleukin-18 mRNA is elevated in subjects with metabolic syndrome and independently associated with fasting glucose

Cited by 17 publications

References 19 publications

Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an Observational Study

Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an Observational Study

Changes in the before and after thyroxine treatment levels of adipose tissue, leptin, and resistin in subclinical hypothyroid patients

Interleukin-18 null mutation increases weight and food intake and reduces energy expenditure and lipid substrate utilization in high-fat diet fed mice

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