Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance.
ABSTRACT Activated innate immunity is thought to be involved in the pathogenesis of metabolic syndrome and type 2 diabetes. Interleukin-18 (IL-18) is a pleiotropic proinflammatory cytokine with important regulatory functions in the innate immune response. We sought to determine whether an elevated IL-18 concentration was a risk predictor for metabolic syndrome in a community population independent of obesity and hyperinsulinemia.
A representative general population, aged 27 to 77 years, without clinical diabetes was studied for clinical and biochemical risk factors for metabolic syndrome. Serum IL-18 concentration measured in 955 subjects correlated with metabolic syndrome traits including body mass index (BMI), waist circumference, triglyceride, high-density lipoprotein (inversely), and fasting glucose and insulin levels (all P<0.001). Mean IL-18 levels rose progressively with the increasing number of metabolic risk factors (ANOVA P<0.001). After adjusting for age, gender, BMI, and insulin levels, increasing IL-18 tertiles were associated with an odds ratio for metabolic syndrome of 1.0, 1.42, and 2.28, respectively (P trend=0.007). The graded risk relation was even stronger in nonobese subjects and not attenuated when adjusted for C-reactive protein and IL-6 levels.
Our findings support the hypothesis that activation of IL-18 is involved in the pathogenesis of the metabolic syndrome.
- SourceAvailable from: Maya Saleh[show abstract] [hide abstract]
ABSTRACT: Inflammation is an important contributor to the development of metabolic disease. Recent work has strongly implicated the inflammasome and caspase-1 as having a pivotal role in the regulation of metabolism, obesity, insulin resistance and cardiovascular disease. Through multiple murine and human studies we now know that the inflammasome can be activated by metabolic triggers in vivo. Clinical studies also reveal the inflammasome to be a potential candidate for therapeutic intervention and provide a clear incentive for future work on this inflammatory pathway.Immunology and Cell Biology advance online publication, 11 February 2014; doi:10.1038/icb.2014.5.Immunology and Cell Biology 02/2014; · 3.93 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Intervention studies on the Mediterranean Diet (MedDiet) have often led to weight loss, which may have contributed to the purported anti-inflammatory effects of the MedDiet. To investigate the impact of the MedDiet consumed under controlled feeding conditions before (-WL) and after weight loss (+WL) on markers of inflammation in men with metabolic syndrome (MetS). Subjects (N = 26, male, 24-65 years) with MetS first consumed a North American control diet for 5 weeks followed by a MedDiet for 5 weeks both in isocaloric feeding conditions. After a 20-week weight loss period in free-living conditions (10 ± 3% reduction in body weight, P < 0.01), participants consumed the MedDiet again under isocaloric-controlled feeding condition for 5 weeks. MedDiet - WL significantly reduced plasma C-reactive protein (CRP) concentrations (-26.1%, P = 0.02) and an arbitrary inflammatory score (-9.9%, P = 0.01) that included CRP, interleukin-6 (IL-6), IL-18, and tumor necrosis factor-α (TNF-α) compared with the control diet. The MedDiet + WL significantly reduced plasma IL-6 (-20.7%) and IL-18 (-15.6%, both P ≤ 0.02) concentrations compared with the control diet but had no further significant impact on plasma CRP concentration. Participants with a reduction in waist circumference ≥8.5 cm after MedDiet + WL showed significantly greater reductions in inflammation markers than those with a change in waist circumference <8.5 cm. Thus, consuming MedDiet even in the absence of weight loss significantly reduces inflammation. However, the degree of waist circumference reduction with weight loss magnifies the impact of the MedDiet on other markers of inflammation associated with MetS in men.Obesity 01/2013; 21(1):51-7. · 3.92 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: BACKGROUND: Metabolic syndrome (coexisting visceral obesity, dyslipidemia, hyperglycemia, and hypertension) is a prominent risk factor for cardiovascular morbidity and mortality, however, its effect on cardiac gene expression pattern is unclear. Therefore, we examined the possible alterations in cardiac gene expression pattern in male Zucker Diabetic Fatty (ZDF) rats, a model of metabolic syndrome. METHODS: Fasting blood glucose, serum insulin, cholesterol and triglyceride levels were measured at 6, 16, and 25 wk of age in male ZDF and lean control rats. Oral glucose tolerance test was performed at 16 and 25 wk of age. At week 25, total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 14921 genes. Expression of selected genes was confirmed by qRT-PCR. RESULTS: Fasting blood glucose, serum insulin, cholesterol and triglyceride levels were significantly increased, glucose tolerance and insulin sensitivity were impaired in ZDF rats compared to leans. In hearts of ZDF rats, 36 genes showed significant up-regulation and 49 genes showed down-regulation as compared to lean controls. Genes with significantly altered expression in the heart due to metabolic syndrome includes functional clusters of metabolism (e.g. 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2; argininosuccinate synthetase; 2-amino-3-ketobutyrate-coenzyme A ligase), structural proteins (e.g. myosin IXA; aggrecan1), signal transduction (e.g. activating transcription factor 3; phospholipase A2; insulin responsive sequence DNA binding protein-1) stress response (e.g. heat shock 70kD protein 1A; heat shock protein 60; glutathione S-transferase Yc2 subunit), ion channels and receptors (e.g. ATPase, (Na+)/K+ transporting, beta 4 polypeptide; ATPase, H+/K+ transporting, nongastric, alpha polypeptide). Moreover some other genes with no definite functional clusters were also changed such as e.g. S100 calcium binding protein A3; ubiquitin carboxy-terminal hydrolase L1; interleukin 18. Gene ontology analysis revealed several significantly enriched functional inter-relationships between genes influenced by metabolic syndrome. CONCLUSIONS: Metabolic syndrome significantly alters cardiac gene expression profile which may be involved in development of cardiac pathologies in the presence of metabolic syndrome.Cardiovascular Diabetology 01/2013; 12(1):16. · 4.21 Impact Factor