68 research outputs found
Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents
Aims/hypothesis: The IL-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine known to antagonise the actions of IL-1. We have previously shown that IL-1Ra is markedly upregulated in the serum of obese patients, is correlated with BMI and insulin resistance, and is overexpressed in the white adipose tissue (WAT) of obese humans. The aim of this study was to examine the role of IL-1Ra in the regulation of glucose homeostasis in rodents. Methods: We assessed the expression of genes related to IL-1 signalling in the WAT of mice fed a high-fat diet, as well as the effect of Il1rn (the gene for IL-1Ra) deletion and treatment with IL-1Ra on glucose homeostasis in rodents. Results: We show that the expression of Il1rn and the gene encoding the inhibitory type II IL-1 receptor was upregulated in diet-induced obesity. The blood insulin:glucose ratio was significantly lower in Il1rn −/− animals, which is compatible with an increased sensitivity to insulin, reinforced by the fact that the insulin content and pancreatic islet morphology of Il1rn −/− animals were normal. In contrast, the administration of IL-1Ra to normal rats for 5days led to a decrease in the whole-body glucose disposal due to a selective decrease in muscle-specific glucose uptake. Conclusions/interpretation: The expression of genes encoding inhibitors of IL-1 signalling is upregulated in the WAT of mice with diet-induced obesity, and IL-1Ra reduces insulin sensitivity in rats through a muscle-specific decrease in glucose uptake. These results suggest that the markedly increased levels of IL-1Ra in human obesity might contribute to the development of insulin resistanc
Elevated Levels of the Anti-Inflammatory Interleukin-1 Receptor Antagonist Precede the Onset of Type 2 Diabetes: The Whitehall II Study
OBJECTIVE—Interleukin-1 receptor antagonist (IL-1Ra), a natural inhibitor of interleukin-1β, has been shown to improve β-cell function and glycemic control in patients with type 2 diabetes. The aim of this study was to investigate whether baseline systemic levels of IL-1Ra are associated with incident type 2 diabetes during more than 10 years of follow-up
Accelerated Increase in Serum Interleukin-1 Receptor Antagonist Starts 6 Years Before Diagnosis of Type 2 Diabetes: Whitehall II Prospective Cohort Study
Correlative studies on the effects of obesity, diabetes and hypertension on gene expression in omental adipose tissue of obese women
The PLIN4 Variant rs8887 Modulates Obesity Related Phenotypes in Humans through Creation of a Novel miR-522 Seed Site
PLIN4 is a member of the PAT family of lipid storage droplet
(LSD) proteins. Associations between seven single nucleotide polymorphisms
(SNPs) at human PLIN4 with obesity related phenotypes were
investigated using meta-analysis followed by a determination if these phenotypes
are modulated by interactions between PLIN4 SNPs and dietary
PUFA. Samples consisted of subjects from two populations of European ancestry.
We demonstrated association of rs8887 with anthropometrics. Meta-analysis
demonstrated significant interactions between the rs8887 minor allele with PUFA
n3 modulating anthropometrics. rs884164 showed interaction with both n3 and n6
PUFA modulating anthropometric and lipid phenotypes. In silico
analysis of the PLIN4 3′UTR sequence surrounding the
rs8887 minor A allele predicted a seed site for the human microRNA-522
(miR-522), suggesting a functional mechanism. Our data showed that a PLIN4
3′UTR luciferase reporter carrying the A allele of rs8887 was reduced in
response to miR-522 mimics compared to the G allele. These results suggest
variation at the PLIN4 locus, and its interaction with PUFA as
a modulator of obesity related phenotypes, acts in part through creation of a
miR-522 regulatory site
Bidirectional crosstalk between neutrophils and adipocytes promotes adipose tissue inflammation
Decreased Fat Mass in Interleukin-1 Receptor Antagonist-Deficient Mice: Impact on Adipogenesis, Food Intake, and Energy Expenditure
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