The complex web of obesity: from genetics to precision medicine

ABSTRACT

Introduction

Obesity is a growing public health concern affecting both children and adults. Since it involves both genetic and environmental components, the management of obesity requires both, an understanding of the underlying genetics and changes in lifestyle. The knowledge of obesity genetics will enable the possibility of precision medicine in anti-obesity medications.

Areas covered

Here, we explore health complications and the prevalence of obesity. We discuss disruptions in energy balance as a symptom of obesity, examining evolutionary theories, its multi-factorial origins, and heritability. Additionally, we discuss monogenic and polygenic obesity, the converging biological pathways, potential pharmacogenomics applications, and existing anti-obesity medications – specifically focussing on the leptin-melanocortin and incretin pathways. Comparisons between childhood and adult obesity genetics are made, along with insights into structural variants, epigenetic changes, and environmental influences on epigenetic signatures.

Expert opinion

With recent advancements in anti-obesity drugs, genetic studies pinpoint new targets and allow for repurposing existing drugs. This creates opportunities for genotype-informed treatment options. Also, lifestyle interventions can help in the prevention and treatment of obesity by altering the epigenetic signatures. The comparison of genetic architecture in adults and children revealed a significant overlap. However, more robust studies with diverse ethnic representation is required in childhood obesity.

KEYWORDS:

• Obesity
• childhood obesity
• pharmacogenomics
• anti-obesity drugs
• precision medicine

Article highlights

• Obesity is a complex multifactorial trait influenced by both genetic and environmental factors.

• Heritability studies indicate a strong genetic component that is facilitated by environmental factors.

• Genetics of childhood and adult obesity largely overlap.

• Genetic studies have shown that both monogenic and polygenic obesity point to the same underlying biological pathway – the leptin-melanocortin pathway.

• The large-scale genetic studies in obesity offers the possibility of identification of potential drug targets, repurposing existing drugs, and genotype-informed treatment strategies.

• Lifestyle intervention focussing on proper diet, physical activity, alcohol consumption, and sleep may help to overcome obesity by inducing alterations at the epigenome level.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17446651.2024.2365785.

Additional information

Funding

This paper was funded by the University PURSE II CDST/SR/PURSE PHASE II/11 provided to Jawaharlal Nehru University, New Delhi, India and Junior Research Fellowship CSIR.