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- Wernstedt, Ingrid, 1978, et al.
(författare)
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A common polymorphism in the interleukin-6 gene promoter is associated with overweight
- 2004
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Ingår i: Int J Obes Relat Metab Disord. ; 28:10, s. 1272-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Human body fat mass is to a large extent genetically determined, but little is known about the susceptibility genes for common obesity. Interleukin-6 (IL-6) suppresses body fat mass in rodents, and IL-6 treatment increases energy expenditure in both rodents and humans. The -174 G/C single-nucleotide polymorphism (SNP) in the IL-6 gene promoter is common in many populations, and -174 C-containing promoters have been found to be weaker enhancers of transcription. Moreover, a SNP at position -572 in the IL-6 promoter has recently been reported to affect transcription. The objective was to investigate the association between the IL-6 gene promoter SNPs and obesity. DESIGN: Trans-sectional association study of IL-6 gene promoter SNPs and indices of obesity. SUBJECTS: Two study populations, the larger one consisting of hypertensive individuals (mean age 57 y, 73% males, n=485) and the other consisting of 20 y younger nonobese healthy females (n=74). MEASUREMENTS: Genotyping for the -174 IL-6 G/C and the -572 G/C SNPs, body mass index (BMI), serum leptin levels, serum IL-6 levels, C-reactive protein, fasting blood glucose and various blood lipids. RESULTS: The common -174 C allele (f(C)=0.46), but not any -572 allele, was associated with higher BMI and higher serum leptin levels in both study populations. In the larger population, there were significant odds ratios for the association of CC (2.13) and GC (1.76) genotypes with overweight (BMI>25 kg/m(2)). Moreover, as the C allele was common, it accounted for a significant population-attributable risk of overweight (12%; CI 2-21%), although its average effect was modest in this sample. CONCLUSION: Genetically determined individual differences in production of IL-6 may be relevant for the regulation of body fat mass.
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| 2. |
- García, Maria C, et al.
(författare)
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Mature-onset obesity in interleukin-1 receptor I knockout mice.
- 2006
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:5, s. 1205-13
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-1 (IL-1) is a major mediator of inflammation that exerts its biological activities through the IL-1 type I receptor (IL-1RI). The body weights of IL-1RI(-/-) mice of both sexes started to deviate from those of wild-type mice at 5-6 months of age and were 20% higher at 9 months of age. Visceral and subcutaneous fat mass, measured by dual-energy X-ray absorptiometry and magnetic resonance imaging, was markedly (1.5- to 2.5-fold) increased. Lean body mass and crown-rump length were also slightly (11 and 5%, respectively) increased, as was serum IGF-I. Obese IL-1RI(-/-) mice were insulin resistant, as evidenced by hyperinsulinemia, decreased glucose tolerance, and insulin sensitivity. To elucidate the mechanisms for the development of obesity, young pre-obese IL-1RI(-/-) mice were investigated. They showed decreased suppression of body weight and food intake in response to systemic leptin treatment. The decreased leptin responsiveness was even more pronounced in older obese animals. Moreover, spontaneous locomotor activity and fat utilization, as measured by respiratory quotient, were decreased in pre-obese IL-1RI(-/-) mice. In conclusion, lack of IL-1RI-mediated biological activity causes mature-onset obesity. This obese phenotype is preceded by decreased leptin sensitivity, fat utilization, and locomotor activity.
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| 3. |
- Jansson, John-Olov, 1954, et al.
(författare)
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Leukemia inhibitory factor reduces body fat mass in ovariectomized mice
- 2006
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Ingår i: Eur J Endocrinol. - : Oxford University Press (OUP). - 0804-4643. ; 154:2, s. 349-54
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Ovariectomized (OVX) mice are known to gain body fat while exposure to estrogens decreases fat mass. We have previously shown that estrogen replacement therapy enhances the expression of receptors for the cytokine, leukemia inhibitory factor (LIF). LIF and other cytokines acting via the gp130 signal transducing receptor have been reported to decrease obesity. In the present study, we investigated whether LIF treatment can reduce obesity in OVX mice. DESIGN: Eight-week-old female C57Bl/6 mice were OVX or sham-operated. The mice were treated with LIF, 30 microg/kg or PBS via daily i.p. injections for 15 days (n = 9-10). METHODS: Dual X-ray absorptiometry and computerized tomography. RESULTS: We found that LIF treatment of OVX mice caused a significant reduction in the weight of white fat depots (P = 0.017) and serum leptin levels (P = 0.011). LIF also caused a significant decrease in brown fat mass (P = 0.036). Treatment with LIF decreased thymus weight but did not affect crown-rump length, femur length, trabecular bone mineral density or the weight of several non-fat organs including the uterus. CONCLUSION: The cytokine, LIF, decreases body fat mass in OVX mice, suggesting that estrogen signaling is not required for this effect.
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| 4. |
- Wernstedt, Ingrid, 1978, et al.
(författare)
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Reduced stress- and cold-induced increase in energy expenditure in interleukin-6-deficient mice.
- 2006
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 291:3
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-6 (IL-6) deficient (-/-) mice develop mature onset obesity. Pharmacological studies have shown that IL-6 has direct lipolytic effects and when administered centrally increases sympathetic outflow. However, the metabolic functions of endogenous IL-6 are not fully elucidated. We aimed to investigate the effect of IL-6 deficiency with respect to cold exposure and cage-switch stress, that is, situations that normally increase sympathetic outflow. Energy metabolism, core temperature, heart rate, and activity were investigated in young preobese IL-6-/- mice by indirect calorimetry together with telemetry. Baseline measurements and the effect of cage-switch stress were investigated at thermoneutrality (30 degrees C) and at room temperature (20 degrees C). The effect of cold exposure was investigated at 4 degrees C. At 30 degrees C, the basal core temperature was 0.6 +/- 0.24 degrees C lower in IL-6-/- compared with wild-type mice, whereas the oxygen consumption did not differ significantly. The respiratory exchange ratio at 20 degrees C was significantly higher and the calculated fat utilization rate was lower in IL-6-/- mice. In response to cage-switch stress, the increase in oxygen consumption at both 30 and 20 degrees C was lower in IL-6-/- than in wild-type mice. The increase in heart rate was lower in IL-6-/- mice at 30 degrees C. At 4 degrees C, both the oxygen consumption and core temperature were lower in IL-6-/- compared with wild-type mice, suggesting a lower cold-induced thermogenesis in IL-6-/- mice. The present results indicate that endogenous IL-6 is of importance for stress- and cold-induced energy expenditure in mice.
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