IL-7 receptor deletion ameliorates diet-induced obesity and insulin resistance in mice.

Abstract

AIM/HYPOTHESIS:

Obesity-induced inflammation plays an important role in the development of insulin resistance and type 2 diabetes. Recent studies have demonstrated that adiposity can be improved by ablating certain inflammatory signalling pathways. Although the IL-7 receptor (IL-7R) is mostly known as a key regulator of T lymphocyte development and homeostasis, its role in obesity and metabolic diseases is unknown. Because IL-7 is markedly increased in the serum of obese individuals and IL-7R (also known as IL7R) is overexpressed in white adipose tissue (WAT) in obesity, we studied the metabolic consequences of genetic Il-7r ablation in mice.

METHODS:

Age-matched Il-7r-deficient (Il-7r KO) and wild-type (WT) littermates were fed a standard chow or high-fat diet (HFD) for 14 weeks. Their serum metabolic variables were measured. The expression of genes and proteins related to insulin resistance and inflammation was evaluated in WAT.

RESULTS:

We demonstrated that Il-7r KO mice exhibited significantly reduced body weight gain and visceral adiposity compared with WT controls on both chow and HFD. The expression of signalling molecules involved in adipogenesis was reduced in the WAT of Il-7r KO mice. We also found that Il-7r KO mice had significantly enhanced glucose homeostasis and insulin sensitivity. Consistent with an improved metabolic phenotype, proinflammatory cytokine production and macrophage infiltration was attenuated in the WAT of Il-7r KO mice.

CONCLUSIONS/INTERPRETATION:

The IL-7R plays an important role in the induction of HFD-induced adipogenesis and insulin resistance in mice.

• Authors: Miyoung Lee, Su Jin Song, Myung-Sook Choi, Rina Yu, Taesun Park
• Journal: Diabetologia (Diabetologia) Vol. 58 Issue 10 Pg. 2361-70 (Oct 2015) ISSN: 1432-0428 [Electronic] Germany
• PMID: 26152662 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Interleukin-7

Topics

• Adipogenesis (genetics)
• Adipose Tissue (metabolism)
• Adiposity (genetics)
• Animals
• Diet, High-Fat
• Inflammation (metabolism)
• Insulin Resistance (genetics)
• Mice
• Mice, Knockout
• Obesity (genetics, metabolism)
• Receptors, Interleukin-7 (genetics, metabolism)