Division of Internal Medicine, Hospital of Bisceglie, Bisceglie, Italy.
Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri", University of Bari Medical School, Bari, Italy.
Eur J Intern Med. 2014 Dec;25(10):865-73. doi: 10.1016/j.ejim.2014.10.012. Epub 2014 Nov 4.
The worldwide obesity epidemic is paralleled by a rise in the incidence of pancreatic disorders ranging from "fatty" pancreas to pancreatitis and cancer. Body fat accumulation and pancreatic dysfunctions have common pathways, mainly acting through insulin resistance and low-grade inflammation, frequently mediated by the epigenome. These mechanisms are affected by lifestyle and by the toxic effects of fat and pollutants. An early origin is common, starting in pediatric age or during the fetal life in response to nutritional factors, endocrine disruptor chemicals (EDCs) or parental exposure to toxics. A "fatty pancreas" is frequent in obese and is able to induce pancreatic damage. The fat is a target of EDCs and of the cytotoxic/mutagenic effects of heavy metals, and is the site of bioaccumulation of lipophilic and persistent pollutants related with insulin resistance and able to promote pancreatic cancer. Increased Body Mass Index (BMI) can act as independent risk factor for a more severe course of acute pancreatitis and obesity is also a well-known risk factor for pancreatic cancer, that is related with BMI, insulin resistance, and duration of exposure to the toxic effects of fat and/or of environmental pollutants. All these mechanisms involve gene-environment interactions through epigenetic factors, and might be manipulated by primary prevention measures. Further studies are needed, pointing to better assess the interplays of modifiable factors on both obesity and pancreatic diseases, and to verify the efficacy of primary prevention strategies involving lifestyle and environmental exposure to toxics.
全球肥胖症的流行伴随着胰腺疾病发病率的上升，从“脂肪”胰腺到胰腺炎和癌症。体脂积累和胰腺功能障碍有共同的途径，主要通过胰岛素抵抗和低度炎症起作用，经常由表观基因组介导。这些机制受生活方式以及脂肪和污染物的毒性影响。一个常见的早期起源始于儿童期或胎儿期，以应对营养因素、内分泌干扰化学物质（EDCs）或父母接触毒物。肥胖症中常见“脂肪胰腺”，能够诱导胰腺损伤。脂肪是 EDCs 和重金属的细胞毒性/诱变作用的靶标，也是与胰岛素抵抗和促进胰腺癌有关的亲脂性和持久性污染物的生物蓄积部位。体重指数（BMI）的增加可以作为急性胰腺炎更严重病程的独立危险因素，肥胖也是胰腺癌的一个众所周知的危险因素，它与 BMI、胰岛素抵抗以及暴露于脂肪和/或环境污染物毒性的时间有关。所有这些机制都涉及通过表观遗传因素进行基因-环境相互作用，并且可以通过初级预防措施进行干预。需要进一步的研究，以更好地评估可改变因素对肥胖症和胰腺疾病的相互作用，并验证涉及生活方式和环境暴露于毒物的初级预防策略的效果。
