Goran Michael I, Alderete Tanya L
Department of Preventive Medicine and Childhood Obesity Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Nestle Nutr Inst Workshop Ser. 2012;73:49-60; discussion p61-6. doi: 10.1159/000341287. Epub 2012 Oct 29.
The prevalence of obesity has increased throughout the last three decades due to genetic, metabolic, behavioral, and environmental factors [1]. Obesity in turn increases risk for a number of metabolic diseases including type 2 diabetes, cardiovascular disease, fatty liver disease and some forms of cancer [1]. Despite the well-known link between obesity and increased morbidity, the mechanism of this remains elusive. Thus, the question 'why does increased body fat cause increased metabolic comorbidities' remains unanswered. By understanding the underlying basis of obesity-associated metabolic diseases, different therapies could be designed to target relevant pathways. Although we lack a full understanding of the underlying mechanisms that result in disease, several putative explanations exist for why fat affects metabolic health. One such theory is based on the anatomic location of fat deposition and ectopic fat accumulation [2]. Specifically, current literature suggests that visceral, liver and skeletal fat accumulation affects organ function and contributes to the development of insulin resistance, fatty liver, and the metabolic syndrome [3]. However, even in individuals matched for body fat and fat distribution, significant differences can exist in metabolic outcomes, and the phenomenon of metabolically healthy obese has been well described [4]. More recent data suggest the alternative hypothesis relating excess adipose tissue to disease risk based on the metabolic function and morphological properties of adipose tissue. In this scenario, excess adipose tissue is hypothesized to contribute to a state of chronic inflammation which promotes development of insulin resistance as well as other metabolic complications by stimulating nuclear factor-ĸB and Jun N-terminal kinase pathways in adipocytes and the liver [5]. In this paper, we will review the hypothesis linking excess adipose tissue to increased disease risk through adipose tissue inflammation.
在过去三十年中，由于遗传、代谢、行为和环境因素，肥胖症的患病率有所上升[1]。肥胖反过来又会增加患多种代谢疾病的风险，包括2型糖尿病、心血管疾病、脂肪肝疾病和某些类型的癌症[1]。尽管肥胖与发病率增加之间的联系众所周知，但其机制仍不清楚。因此，“为什么体脂增加会导致代谢合并症增加”这个问题仍然没有答案。通过了解肥胖相关代谢疾病的潜在基础，可以设计不同的疗法来针对相关途径。虽然我们对导致疾病的潜在机制缺乏全面的了解，但对于脂肪为何影响代谢健康存在几种假定的解释。一种这样的理论基于脂肪沉积的解剖位置和异位脂肪堆积[2]。具体而言，当前文献表明，内脏、肝脏和骨骼肌脂肪堆积会影响器官功能，并导致胰岛素抵抗、脂肪肝和代谢综合征的发展[3]。然而，即使在体脂和脂肪分布相匹配的个体中，代谢结果也可能存在显著差异，并且代谢健康肥胖的现象已得到充分描述[4]。最近的数据提出了另一种假设，即基于脂肪组织代谢功能和形态学特性，将过多的脂肪组织与疾病风险联系起来。在这种情况下，过多的脂肪组织被认为会导致慢性炎症状态，通过刺激脂肪细胞和肝脏中的核因子-κB和Jun N末端激酶途径，促进胰岛素抵抗以及其他代谢并发症的发展[5]。在本文中，我们将综述通过脂肪组织炎症将过多的脂肪组织与疾病风险增加联系起来的假设。
