Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.
Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey.
Adv Exp Med Biol. 2024;1460:167-198. doi: 10.1007/978-3-031-63657-8_6.
Obesity-related co-morbidities decrease life quality, reduce working ability, and lead to early death. In the adult population, eating addiction manifests with excessive food consumption and the unrestrained overeating behavior, which is associated with increased risk of morbidity and mortality and defined as the binge eating disorder (BED). This hedonic intake is correlated with fat preference and the total amount of dietary fat consumption is the most potent risk factor for weight gain. Long-term BED leads to greater sensitivity to the rewarding effects of palatable foods and results in obesity fatefully. Increased plasma concentrations of non-esterified free fatty acids and lipid-overloaded hypertrophic adipocytes may cause insulin resistance. In addition to dietary intake of high-fat diet, sedentary lifestyle leads to increased storage of triglycerides not only in adipose tissue but also ectopically in other tissues. Lipid-induced apoptosis, ceramide accumulation, reactive oxygen species overproduction, endoplasmic reticulum stress, and mitochondrial dysfunction play role in the pathogenesis of lipotoxicity. Food addiction and BED originate from complex action of dopaminergic, opioid, and cannabinoid systems. BED may also be associated with both obesity and major depressive disorder. For preventing morbidity and mortality, as well as decreasing the impact of obesity-related comorbidities in appropriately selected patients, opiate receptor antagonists and antidepressant combination are recommended. Pharmacotherapy alongside behavioral management improves quality of life and reduces the obesity risk; however, the number of licensed drugs is very few. Thus, stereotactic treatment is recommended to break down the refractory obesity and binge eating in obese patient. As recent applications in the field of non-invasive neuromodulation, transcranial magnetic stimulation and transcranial direct current stimulation are thought to be important in image-guided deep brain stimulation in humans. Chronic overnutrition most likely provides repetitive and persistent signals that up-regulate inhibitor of nuclear factor kappa B (NF-κB) kinase beta subunit/NF-κB (IKKβ/NF-κB) in the hypothalamus before the onset of obesity. However, how the mechanisms of high-fat diet-induced peripheral signals affect the hypothalamic arcuate nucleus remain largely unknown.
肥胖相关的合并症降低生活质量、降低工作能力，并导致早逝。在成年人群中，进食成瘾表现为过度进食和不受控制的暴饮暴食行为，这与发病率和死亡率增加有关，并被定义为暴食障碍（BED）。这种享乐性摄入与脂肪偏好相关，而总膳食脂肪摄入量是体重增加的最强风险因素。长期的 BED 导致对美味食物的奖赏效应更加敏感，并最终导致肥胖。血浆中非酯化游离脂肪酸浓度增加和脂质超负荷肥大脂肪细胞可能导致胰岛素抵抗。除了高脂肪饮食的摄入外，久坐的生活方式不仅导致脂肪组织中甘油三酯的储存增加，还导致其他组织中甘油三酯的异位储存。脂质诱导的细胞凋亡、神经酰胺积累、活性氧过度产生、内质网应激和线粒体功能障碍在脂毒性发病机制中起作用。食物成瘾和 BED 源于多巴胺能、阿片能和大麻素系统的复杂作用。BED 也可能与肥胖和重度抑郁症有关。为了预防发病率和死亡率，并降低适当选择的患者肥胖相关合并症的影响，建议使用阿片受体拮抗剂和抗抑郁药联合治疗。药物治疗联合行为管理可提高生活质量并降低肥胖风险；然而，获得许可的药物数量非常有限。因此，建议对肥胖患者进行立体定向治疗以打破难治性肥胖和暴食。作为非侵入性神经调节领域的最新应用，经颅磁刺激和经颅直流电刺激被认为在人类影像引导下深部脑刺激中很重要。慢性营养过剩很可能在肥胖发生前提供重复和持续的信号，上调下丘脑核因子 kappa B（NF-κB）激酶β亚单位/NF-κB（IKKβ/NF-κB）。然而，高脂肪饮食诱导的外周信号的机制如何影响下丘脑弓状核仍知之甚少。
