Assistance Publique-Hôpitaux de Paris, Reference Center for Rare Diseases (PRADORT, Prader-Willi Syndrome and Other Rare Forms of Obesity with Eating Behavior Disorders), Nutrition Department, Pitié-Salpêtrière Hospital, Paris, France.
Sorbonne Université, INSERM, Nutrition and Obesity: Systemic Approaches (NutriOmics) Research Unit, Paris, France.
Eur J Endocrinol. 2020 Nov;183(5):R149-R166. doi: 10.1530/EJE-20-0363.
Obesity, defined by an excess of body fat impacting on health, is a complex disease resulting from the interaction between many genetic/epigenetic factors and environmental triggers. For some clinical situations with severe obesity, it has been possible to classify these obesity forms according to the molecular alterations. These include: (i) syndromic obesity, which associates severe early-onset obesity with neurodevelopmental disorders and/or polymalformative syndrome and (ii) non-syndromic monogenic obesity, due to gene variants most often located in the leptin-melanocortin pathway. In addition to severe obesity, patients affected by these diseases display complex somatic conditions, eventually including obesity comorbidities, neuropsychological and psychiatric disorders. These conditions render the clinical management of these patients particularly challenging. Patients' early diagnosis is critical to allow specialized and multidisciplinary care, with a necessary interaction between the health and social sectors. Up to now, the management of genetic obesity was only based, above all, on controlling the patient's environment, which involves limiting access to food, ensuring a reassuring daily eating environment that limits impulsiveness, and the practice of adapted, supported, and supervised physical activity. Bariatric surgery has also been undertaken in genetic obesity cases with uncertain outcomes. The context is rapidly changing, as new innovative therapies are currently being tested both for syndromic and monogenic forms of obesity. This review focuses on care management and new therapeutic opportunities in genetic obesity, including the use of the melanocortin 4 agonist, setmelanotide. The results from ongoing trials will hopefully pave the way to a future precision medicine approach for genetic obesity.
肥胖是指体内脂肪过多影响健康的一种病症，是由许多遗传/表观遗传因素与环境触发因素相互作用而导致的一种复杂疾病。对于某些严重肥胖的临床情况，已经有可能根据分子改变对这些肥胖形式进行分类。这些包括：（i）综合征性肥胖，其将严重的早发性肥胖与神经发育障碍和/或多畸形综合征相关联；（ii）非综合征性单基因肥胖，是由于基因变异，这些变异通常位于瘦素-黑素皮质素途径中。除了严重肥胖外，患有这些疾病的患者还表现出复杂的躯体状况，最终包括肥胖合并症、神经心理和精神障碍。这些情况使得这些患者的临床管理极具挑战性。患者的早期诊断对于允许进行专门的多学科护理至关重要，需要卫生和社会部门之间进行必要的互动。到目前为止，遗传肥胖的管理主要基于控制患者的环境，包括限制食物的获取、确保令人安心的日常饮食环境以限制冲动，以及进行适应性、支持性和监督性的体育活动。在遗传肥胖的情况下，还进行了减肥手术，但结果不确定。目前，正在对综合征性和单基因肥胖形式进行新的创新疗法的测试，这种情况的背景正在迅速变化。本综述重点介绍了遗传肥胖的护理管理和新的治疗机会，包括使用黑皮质素 4 激动剂 setmelanotide。正在进行的试验的结果有望为遗传肥胖的未来精准医疗方法铺平道路。
