Abstract
Although interleukin (IL)-7 is mostly known as a key regulator of lymphocyte homeostasis, we recently demonstrated that it also contributes to body weight regulation through a hypothalamic control. Previous studies have shown that IL-7 is produced by the human obese white adipose tissue (WAT) yet its potential role on WAT development and function in obesity remains unknown. Here, we first show that transgenic mice overexpressing IL-7 have reduced adipose tissue mass associated with glucose and insulin resistance. Moreover, in the high-fat diet (HFD)-induced obesity model, a single administration of IL-7 to C57BL/6 mice is sufficient to prevent HFD-induced WAT mass increase and glucose intolerance. This metabolic protective effect is accompanied by a significant decreased inflammation in WAT. In lymphocyte-deficient HFD-fed SCID mice, IL-7 injection still protects from WAT mass gain. However, IL-7-triggered resistance against WAT inflammation and glucose intolerance is lost in SCID mice. These results suggest that IL-7 regulates adipose tissue mass through a lymphocyte-independent mechanism while its protective role on glucose homeostasis would be relayed by immune cells that participate to WAT inflammation. Our observations establish a key role for IL-7 in the complex mechanisms by which immune mediators modulate metabolic functions.
Highlights
The disproportionate lack of white adipose tissue (WAT) in lipodystrophy and the excessive gain of WAT in obesity are both frequently associated with severe insulin resistance [1], [2]
White Adipose Tissue Mass and Sensitivity to Insulin are Impaired in IL-7 Overexpressing Mice As a first step to study whether IL-7 might impact on the adipose tissue, we used IL-7 transgenic mice, in which overexpression is driven by the human keratin-14 (K14) promoter (Tg IL-7; [25])
Interleukin-7 (IL-7) is an immune cytokine that is critical for lymphocyte development and homeostasis [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], recently found to be oversecreted by the visceral adipose tissue in obese subjects [9]
Summary
The disproportionate lack of white adipose tissue (WAT) in lipodystrophy and the excessive gain of WAT in obesity are both frequently associated with severe insulin resistance [1], [2]. This highlights the central role for adipose tissue as an essential organ for proper metabolic regulation. IL-7 has recently been identified as a new adipokine whose expression and secretion are increased in the obese human adipose tissue [9] Whether this endogenous production of IL-7 has any physiological function in adipose tissue and metabolism is still unknown
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