Interleukin‐15 in obesity and metabolic dysfunction: current understanding and future perspectives

Abstract

Obesity rises rapidly and is a major health concern for modern people. Importantly, it is a major risk factor in the development of numerous chronic diseases such as type 2 diabetes mellitus (T2DM). Recently, interleukin (IL)-15 has attracted considerable attention as a potential regulator for the prevention and/or treatment of obesity and T2DM. The beneficial effects include increased loss of fat mass and body weight, improved lipid and glucose metabolism, reduced white adipose tissue inflammation, enhanced mitochondrial function, alterations in the composition of muscle fibres and gut bacterial and attenuated endoplasmic reticulum stress. Although these beneficial effects are somewhat controversial, IL-15, exogenously delivered or endogenously produced, may be a promising target in the prevention and treatment of obesity and T2DM.

Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives

“…83,84 Importantly, obese subjects have lower circulating IL-15 relative to lean individuals and circulating IL-15 is inversely related to trunk fat mass and per cent body fat; these findings support the possibility that there exists a skeletal muscle-blood-adipose IL-15 axis in humans associated with obesity. [86][87][88] It is important to note that while these findings support a role for IL-15 in determining insulin sensitivity and control of obesity, the molecular mechanism(s) by which Il-15 ameliorates the detrimental effects of TNF-α have not been fully established. [86][87][88] Such "low grade systemic inflammation" is characterized by a two-to threefold increase in the systemic concentrations of cytokines such as TNF-α, an inflammatory marker noted as critical in the development of insulin resistance and muscle wasting in diabetic patients and decreased production of adiponectin.…”

“…[80][81][82] The beneficial role of IL-15 on the prevention of obesity may also include its effects on glucose homoeostasis and insulin resistance. [86][87][88] Such "low grade systemic inflammation" is characterized by a two-to threefold increase in the systemic concentrations of cytokines such as TNF-α, an inflammatory marker noted as critical in the development of insulin resistance and muscle wasting in diabetic patients and decreased production of adiponectin. 83,84 Importantly, obese subjects have lower circulating IL-15 relative to lean individuals and circulating IL-15 is inversely related to trunk fat mass and per cent body fat; these findings support the possibility that there exists a skeletal muscle-blood-adipose IL-15 axis in humans associated with obesity.…”

“…[80][81][82] In HFD-mice, hydrodynamic delivery of a plasmid expressing IL-15 resulted in improved insulin sensitivity, as evidenced by reduced fasting glucose levels and decreased blood insulin levels. [86][87][88] In contrast, overexpression of IL-15 stimulates adiponectin secretion, lowers the concentration of circulating leptin with a concerted loss of intra-abdominal fat mass and counteracts TNF-α action on muscle protein degradation. 85 In addition, it has been demonstrated that the production of IL-15 induced by physical activity may help to attenuate or even suppress the negative effects of tumor necrosis factor-alpha (TNF-α) in obese and diabetic subjects, in whom a low-grade systemic inflammatory state exists, by regulating blood glucose and lipid levels and diminishing proteolysis in striated muscle.…”

Intact regulation of muscle expression and circulating levels of myokines in response to exercise in patients with type 2 diabetes

“…Interleukin‐15 (IL‐15) is another presumed myokine, which is believed to play a role in muscle growth, lipid and glucose metabolism, enhanced mitochondrial function and reduced fat mass (Duan et al. ). Acute exercise has been shown to increase the circulating levels of IL‐15 in healthy, lean, and obese individuals (Riechman et al.…”

“…However, IL-6 infusion into patients with T2D did not improve insulin sensitivity (Harder-Lauridsen et al 2014). Interleukin-15 (IL-15) is another presumed myokine, which is believed to play a role in muscle growth, lipid and glucose metabolism, enhanced mitochondrial function and reduced fat mass (Duan et al 2017). Acute exercise has been shown to increase the circulating levels of IL-15 in healthy, lean, and obese individuals (Riechman et al 2004;Tamura et al 2011;Christiansen et al 2013).…”