The association of interleukin-18 genotype and serum levels with metabolic risk factors for cardiovascular disease

Evans, Juliet; Collins, Malcolm; Jennings, Courtney; Merwe, Lize van der; Söderström, Ingegerd; Olsson, Tommy; Levitt, Naomi; Lambert, Estelle V.; Goedecke, Julia H.

doi:10.1530/eje-07-0463

Cited by 49 publications

(35 citation statements)

References 51 publications

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“…Perhaps reminiscent of obesity-related leptin resistance, leukocytes from patients with obesity or type 2 diabetes are resistant to IL-18 (Zilverschoon et al, 2008). Polymorphisms of the IL-18 gene or its receptor have been associated with obesity (Melen et al, 2010) and metabolic syndrome disorders (Evans et al, 2007; Koch et al, 2011; Presta et al, 2009) in humans. The present and previous (Netea et al, 2006; Zorrilla et al, 2007) loss-of-function and pharmacological results support the hypothesis that endogenous IL-18 suppresses appetite and promotes energy expenditure and lipid fuel substrate utilization and may do so not only during sickness, but also in healthy adults.…”

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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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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“…1,4 Differences in these relationships may be explained, in part, by ethnic differences in the distribution of inflammatory gene polymorphisms and inflammatory gene expression, 5,6 insulin sensitivity, 6 obesity risk, dietary fat and specific fatty acid intake, and serum lipid concentrations between black and white SA women. 1,7 The functional -308 G4A polymorphism within the promoter region of the TNFA gene is in close proximity to the TNFA -238 G4A polymorphism (rs361525).…”

Section: Introductionmentioning

confidence: 99%

The tumor necrosis factor-α gene -238 G>A polymorphism, dietary fat intake, obesity risk and serum lipid concentrations in black and white South African women

et al. 2012

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BACKGROUND/OBJECTIVES: This study explored interactions between dietary fat intake and the tumor necrosis factor-a gene (TNFA) -238 G4A polymorphism (rs361525) on adiposity and serum lipid concentrations in apparently healthy premenopausal black and white South African (SA) women. SUBJECTS/METHODS: Normal-weight (N ¼ 107) and obese (N ¼ 120) black, and normal-weight (N ¼ 89) and obese (N ¼ 62) white SA women underwent measurements of body composition, fasting lipids and dietary intake, and were genotyped for the -238 G4A polymorphism. RESULTS: Black women had a higher -238 GA genotype frequency than white women (Po0.001), but there were no differences between body mass index groups. Black women with the -238 A allele had a greater body fat % than those with the GG genotype (Po0.001). Further, in black women, with increasing polyunsaturated:saturated fat ratio and omega-6 (n-6):omega-3 (n-3) ratio, high-density lipoprotein-cholesterol (HDL-C) concentrations decreased, and total cholesterol (T-C):HDL-C ratio increased in those with the GA genotype but not the GG genotype. In addition, with increasing n-3 polyunsaturated fatty acid intake (percentage of total energy intake, %E), T-C:HDL-C ratio decreased in those with the GA genotype, but not in those with the GG genotype. In white SA women, with increasing eicosapentaenoic acid (%E) intake, low-density lipoprotein-cholesterol concentrations decreased in those with the GG genotype but not the GA genotype. CONCLUSIONS: The -238 G4A polymorphism was associated with body fatness in black women. Interactions between -238 G4A genotypes and dietary fat intake on serum lipids and adiposity differed depending on dietary fat intake, but those for serum lipids were not the same in black and white SA women.

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“…Further, we showed that the minor C allele was associated with elevated blood pressure in black women, independent of circulating IL-18 levels, age, and VAT [46].…”

Section: Ethnic Differences In Inflammatory Genes and Relation To Rismentioning

confidence: 68%

Inflammation in Relation to Cardiovascular Disease Risk: Comparison of Black and White Women in the United States, United Kingdom, and South Africa

Evans

Goedecke

2011

Curr Cardiovasc Risk Rep

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Ethnic differences in the prevalence of cardiovascular disease and type 2 diabetes mellitus and associated metabolic risk factors have been shown in both developed and developing countries. This review explores the hypothesis that ethnic differences in the inflammatory response are associated with the disparities in disease risk in black and white women from South Africa, the United States of America, and the United Kingdom. Higher inflammatory profiles at the genetic, adipose tissue, and circulating level have been reported in black compared to white women but do not explain the disparity in disease risk between black and white women. Ethnic differences in inflammation and their association with disease risk have been shown to be partly mediated by differences in underlying genetic variation, body fat and its distribution, socioeconomic status and lifestyle factors, as well as their interactions.

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The association of interleukin-18 genotype and serum levels with metabolic risk factors for cardiovascular disease

Cited by 49 publications

References 51 publications

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

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

The tumor necrosis factor-α gene -238 G>A polymorphism, dietary fat intake, obesity risk and serum lipid concentrations in black and white South African women

Inflammation in Relation to Cardiovascular Disease Risk: Comparison of Black and White Women in the United States, United Kingdom, and South Africa

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