Interleukin-1 beta: a potential link between stress and the development of visceral obesity

Abstract

BackgroundA disproportionate amount of body fat within the abdominal cavity, otherwise known as visceral obesity, best predicts the negative health outcomes associated with high levels body fat. Growing evidence suggests that repeated activation of the stress response can favor visceral fat deposition and that visceral obesity may induce low-grade, systemic inflammation which is etiologically linked to the pathogenesis of obesity related diseases such as cardiovascular disease and type 2 diabetes. While the obesity epidemic has fueled considerable interest in these obesity-related inflammatory diseases, surprisingly little research is currently focused on understanding the functions of inflammatory proteins in healthy, non-obese white adipose tissue (WAT) and their possible role in modulating stress-induced shifts in body fat distribution.HypothesisThe current review presents evidence in support the novel hypothesis that stress-evoked interleukin-1 beta (IL-1β) signaling within subcutaneous adipose tissue, when repeatedly induced, contributes toward the development of visceral obesity. It is suggested that because acute stressor exposure differentially increases IL-1β levels within subcutaneous adipose relative to visceral adipose tissue in otherwise healthy, non-obese rats, repeated induction of this response may impair the ability of subcutaneous adipose tissue to uptake energy substrates, synthesize and retain triglycerides, and/or adapt to positive energy balance via hyperplasia. Consequently, circulating energy substrates may be disproportionately shunted to visceral adipose tissue for storage, thus driving the development of visceral obesity.ConclusionsThis review establishes the following key points: 1) body fat distribution outweighs the importance of total body fat when predicting obesity-related disease risk; 2) repeated exposure to stress can drive the development of visceral obesity independent of changes in body weight; 3) because of the heterogeneity of WAT composition and function, an accurate understanding of WAT responses requires sampling multiple WAT depots; 4) acute, non-pathogenic stressor exposure increases WAT IL-1β concentrations in a depot specific manner suggesting an adaptive, metabolic role for this cytokine; however, when repeated, stress-induced IL-1β in non-visceral WAT may result in functional impairments that drive the development of stress-induced visceral obesity.

Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease

“…All these mechanisms are operative in human adipose tissue and appear to be more pronounced in human visceral compared to subcutaneous tissue [19]. Repeated stress-induced IL-1b production in white adipose tissue may result in functional impairments that drive the development of stress-induced visceral obesity [93].…”

Inhibition of the nucleotide-binding domain, leucine-rich containing family, pyrin-domain containing 3 inflammasome reduces the severity of experimentally induced acute pancreatitis in obese mice

“…Obesity is associated with a state of chronic low-grade inflammation and increased circulating inflammatory cytokines, which are linked to the pathogenesis of obesity-related diseases, such as cardiovascular disease and type-2 diabetes [15–18]. Coincidental with this chronic inflammation, NLRP3 inflammasome activity is increased in obese individuals, as a result of adipocyte hypertrophy, hypoxia due to poor vascularization of expanding adipose tissue and necrotic cell death, leading to reactive oxygen species (ROS) production and the release of free fatty acids (FFAs) and inflammatory cytokines [19–21].…”

Gene by stress genome-wide interaction analysis and path analysis identify EBF1 as a cardiovascular and metabolic risk gene

“…7,8 The repeated exposure to psychosocial stress has been linked to the development of visceral obesity. 9 Methylation studies have also demonstrated that distressing life events can alter the expression of variants through effects on promoter DNA methylation. 10 These findings support the need to understand the relationship between genetic susceptibility, psychosocial stress, and metabolic factors acting in combination to increase the risk of CVD.…”