Background

Obesity is a multifactorial chronic disease with a high, increasing worldwide prevalence. Genetic causes account for 7% of the cases in children with extreme obesity.

Data sources

This narrative review was conducted by searching for papers published in the PubMed/MEDLINE, Embase and SciELO databases and included 161 articles. The search used the following search terms: “obesity”, “obesity and genetics”, “leptin”, “Prader-Willi syndrome”, and “melanocortins”. The types of studies included were systematic reviews, clinical trials, prospective cohort studies, cross-sectional and prospective studies, narrative reviews, and case reports.

Results

The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body weight. However, several important aspects of the pathophysiology of obesity remain unknown. Genetic causes of obesity can be grouped into syndromic, monogenic, and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years, hyperphagia, or a family history of extreme obesity. A microarray study, an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this purpose. There are three therapeutic levels: lifestyle modifications, pharmacological treatment, and bariatric surgery.

Conclusions

Genetic study technologies are in constant development; however, we are still far from having a personalized approach to genetic causes of obesity. A significant proportion of the affected individuals are associated with genetic causes; however, there are still barriers to its approach, as it continues to be underdiagnosed.

Video Abstract (MP4 1041807 KB)

中文翻译：

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肥胖遗传原因的全面回顾

背景

肥胖是一种多因素慢性疾病，其患病率在全球范围内呈上升趋势。遗传原因占儿童极度肥胖病例的 7%。

数据源

这项叙述性综述是通过检索 PubMed/MEDLINE、Embase 和 SciELO 数据库中发表的论文进行的，包括 161 篇文章。搜索使用了以下搜索词：“肥胖”、“肥胖与遗传学”、“瘦素”、“普拉德威利综合征”和“黑皮质素”。包括的研究类型包括系统评价、临床试验、前瞻性队列研究、横断面和前瞻性研究、叙述性评价和病例报告。

结果

瘦素-黑皮质素途径主要负责食欲和体重的调节。然而，肥胖病理生理学的几个重要方面仍然未知。肥胖的遗传原因可分为综合征性、单基因性和多基因性原因，应对 5 岁之前患有极度肥胖、食欲过盛或有极度肥胖家族史的儿童进行评估。为此目的，应进行微阵列研究、黑皮质素 4 型受体基因突变和瘦素水平分析。治疗分为三个级别：生活方式改变、药物治疗和减肥手术。

结论

基因研究技术在不断发展；然而，我们还远远没有找到针对肥胖遗传原因的个性化方法。很大一部分受影响的个体与遗传原因有关；然而，其方法仍然存在障碍，因为它仍然未被充分诊断。

视频摘要 (MP4 1041807 KB)