Speaker Kristin J, Fleshner Monika
Department of Integrative Physiology, University of Colorado at Boulder, 80309, USA.
BMC Physiol. 2012 Jun 27;12:8. doi: 10.1186/1472-6793-12-8.
A 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.
The 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.
This 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.
腹腔内过多的体脂，即内脏肥胖，最能预示与高水平体脂相关的负面健康结果。越来越多的证据表明，应激反应的反复激活会促进内脏脂肪沉积，且内脏肥胖可能会引发低度全身性炎症，这种炎症在病因上与肥胖相关疾病（如心血管疾病和2型糖尿病）的发病机制有关。尽管肥胖流行引发了人们对这些与肥胖相关的炎症性疾病相当大的兴趣，但令人惊讶的是，目前很少有研究专注于了解炎症蛋白在健康、非肥胖白色脂肪组织（WAT）中的功能及其在调节应激诱导的体脂分布变化中可能发挥的作用。
本综述提供了证据支持这一新假设，即反复诱导时，皮下脂肪组织中应激诱发的白细胞介素-1β（IL-1β）信号传导有助于内脏肥胖的发展。研究表明，在原本健康、非肥胖的大鼠中，急性应激源暴露会使皮下脂肪组织中的IL-1β水平相对于内脏脂肪组织有差异地升高，这种反应的反复诱导可能会损害皮下脂肪组织摄取能量底物、合成和储存甘油三酯以及/或通过增生适应正能量平衡的能力。因此，循环中的能量底物可能会不成比例地分流到内脏脂肪组织进行储存，从而推动内脏肥胖的发展。
本综述确立了以下要点：1）在预测肥胖相关疾病风险时，体脂分布比总体脂的重要性更大；2）反复暴露于应激可独立于体重变化推动内脏肥胖的发展；3）由于WAT组成和功能的异质性，准确了解WAT反应需要对多个WAT储存部位进行采样；4）急性、非致病性应激源暴露以储存部位特异性方式增加WAT中IL-1β浓度，表明该细胞因子具有适应性代谢作用；然而，反复应激诱导的非内脏WAT中的IL-1β可能导致功能障碍，从而推动应激诱导的内脏肥胖的发展。
