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Interleukin-37 treatment of mice with metabolic syndrome improves insulin sensitivity and reduces pro-inflammatory cytokine production in adipose tissue.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2018 Sep 14; Vol. 293 (37), pp. 14224-14236. Date of Electronic Publication: 2018 Jul 13. - Publication Year :
- 2018
-
Abstract
- Obesity and the metabolic syndrome are characterized by chronic, low-grade inflammation mainly originating from expanding adipose tissue and resulting in inhibition of insulin signaling and disruption of glycemic control. Transgenic mice expressing human interleukin 37 (IL-37), an anti-inflammatory cytokine of the IL-1 family, are protected against metabolic syndrome when fed a high-fat diet (HFD) containing 45% fat. Here, we examined whether treatment with recombinant IL-37 ameliorates established insulin resistance and obesity-induced inflammation. WT mice were fed a HFD for 22 weeks and then treated daily with IL-37 (1 μg/mouse) during the last 2 weeks. Compared with vehicle only-treated mice, IL-37-treated mice exhibited reduced insulin in the plasma and had significant improvements in glucose tolerance and in insulin content of the islets. The IL-37 treatment also increased the levels of circulating IL-1 receptor antagonist. Cultured adipose tissues revealed that IL-37 treatment significantly decreases spontaneous secretions of IL-1β, tumor necrosis factor α (TNFα), and C X C motif chemokine ligand 1 (CXCL-1). We also fed mice a 60% fat diet with concomitant daily IL-37 for 2 weeks and observed decreased secretion of IL-1β, TNFα, and IL-6 and reduced intracellular levels of IL-1α in the liver and adipose tissue, along with improved plasma glucose clearance. Compared with vehicle treatment, these IL-37-treated mice had no apparent weight gain. In human adipose tissue cultures, the presence of 50 pm IL-37 reduced spontaneous release of TNFα and 50% of lipopolysaccharide-induced TNFα. These findings indicate that IL-37's anti-inflammatory effects can ameliorate established metabolic disturbances during obesity.<br /> (© 2018 Ballak et al.)
- Subjects :
- Animals
Biomarkers blood
Diet, High-Fat
Glucose Tolerance Test
Humans
Interleukin-1 genetics
Metabolic Syndrome metabolism
Metabolic Syndrome physiopathology
Mice
Mice, Transgenic
Receptors, Interleukin-1 Type I antagonists & inhibitors
Recombinant Proteins genetics
Recombinant Proteins therapeutic use
Adipose Tissue metabolism
Cytokines biosynthesis
Inflammation Mediators metabolism
Insulin Resistance
Interleukin-1 therapeutic use
Metabolic Syndrome drug therapy
Obesity physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 293
- Issue :
- 37
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30006351
- Full Text :
- https://doi.org/10.1074/jbc.RA118.003698