Yilmaz Bayram, Erdogan Cihan Suleyman, Sandal Suleyman, Kelestimur Fahrettin, Carpenter David O
Department of Physiology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey.
Izmir Biomedicine and Genome Center, Izmir, Turkey.
Neuroendocrinology. 2025;115(1):72-100. doi: 10.1159/000542901. Epub 2024 Dec 2.
Obesity is a major risk factor for noncommunicable diseases and is associated with a reduced life expectancy of up to 20 years, as well as with other consequences such as unemployment and increased economic burden for society. It is a multifactorial disease, and physiopathology of obesity involves dysregulated calorie utilization and energy balance, disrupted homeostasis of appetite and satiety, lifestyle factors including sedentary lifestyle, lower socioeconomic status, genetic predisposition, epigenetics, and environmental factors. Some endocrine-disrupting chemicals (EDCs) have been proposed as "obesogens" that stimulate adipogenesis leading to obesity. In this review, definition of obesogens, their adverse effects, underlying mechanisms, and metabolic implications will be updated and discussed.
Disruption of lipid homeostasis by EDCs involves multiple mechanisms including increase in the number and size of adipocytes, disruption of endocrine-regulated adiposity and metabolism, alteration of hypothalamic regulation of appetite, satiety, food preference and energy balance, and modification of insulin sensitivity in the liver, skeletal muscle, pancreas, gastrointestinal system, and the brain. At a cellular level, obesogens can exert their endocrine disruptive effects by interfering with peroxisome proliferator-activated receptors and steroid receptors. Human exposure to chemical obesogens mainly occurs by ingestion and, to some extent, by inhalation and dermal uptake, usually in an unconscious manner. Persistent pollutants are lipophilic features; thus, they bioaccumulate in adipose tissue.
Although there are an increasing number of reports studying the effects of obesogens, their mechanisms of action remain to be elucidated. In addition, epidemiological studies are needed in order to evaluate human exposure to obesogens.
肥胖是非传染性疾病的主要风险因素，与预期寿命缩短多达20年相关，还与其他后果有关，如失业和社会经济负担增加。肥胖是一种多因素疾病，其病理生理学涉及热量利用和能量平衡失调、食欲和饱腹感的内稳态破坏、包括久坐不动的生活方式、较低的社会经济地位、遗传易感性、表观遗传学以及环境因素等生活方式因素。一些内分泌干扰化学物质（EDCs）已被提出作为“致肥胖物”，可刺激脂肪生成导致肥胖。在本综述中，将更新并讨论致肥胖物的定义、其不良影响、潜在机制和代谢影响。
EDCs对脂质稳态的破坏涉及多种机制，包括脂肪细胞数量和大小增加、内分泌调节的肥胖和代谢紊乱、下丘脑对食欲、饱腹感、食物偏好和能量平衡的调节改变，以及肝脏、骨骼肌、胰腺、胃肠道系统和大脑中胰岛素敏感性的改变。在细胞水平上，致肥胖物可通过干扰过氧化物酶体增殖物激活受体和类固醇受体发挥其内分泌干扰作用。人类接触化学致肥胖物主要通过摄入，在一定程度上也通过吸入和皮肤吸收，通常是无意识的。持久性污染物具有亲脂性特征；因此，它们在脂肪组织中生物蓄积。
尽管越来越多的报告研究致肥胖物的影响，但其作用机制仍有待阐明。此外，需要进行流行病学研究以评估人类接触致肥胖物的情况。
