Obesity genes

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Although physical inactivity and consuming energy-dense foods are commonly identified as the main culprits behind obesity and overweight, there exist additional factors such as hormonal and genetic factors that can heighten the likelihood of developing obesity.

The causes of obesity, including environmental and lifestyle factors, as well as genetic predisposition, have been extensively researched by scientists. Currently, significant attention is being paid to examining the interplay between genes and the environment, which may be responsible for the escalating prevalence of obesity across the globe.

Obesity-related genes have been identified through recent advancements in genetic testing. Causative genes for obesity include Leptin (LEP), the leptin receptor (LEPR), proopiomelanocortin (POMC), prohormone convertase 1 (PCSK1), the melanocortin 4 receptor (MC4R), single-minded homolog 1 (SIM1), brain-derived neurotrophic factor (BDNF), and the neurotrophic tyrosine kinase receptor type 2 gene (NTRK2).

White adipose tissue secretes a protein called Leptin, which is encoded by a gene on chromosome 7 in humans. Leptin has the ability to cross the blood-brain barrier and bind to the presynaptic GABAergic neurons of the hypothalamus. This results in a decrease in appetite and an increase in energy expenditure. The arcuate nucleus of the hypothalamus is where Leptin binds to its receptor and inhibits the neuropeptide Y (NPY)/agouti-related protein (AgRP) pathway.

The POMC gene, located on chromosome 2 in humans, plays a role in suppressing appetite. It affects the leptin-melanocortin system by producing ACTH and alpha-MSH, which are derived from the POMC protein. When there is a deficiency of POMC, these hormones are not produced, resulting in increased hunger, a decrease in resting metabolic rate, and severe obesity with red hair and pale skin.

Before advanced genetic testing and next generation sequencing (NGS), the melanocortin-4 receptor (MC4R) gene was found in approximately 4% of childhood obesity cases and is now recognized as the most frequently associated gene.

The discovery of FTO as the first obesity-susceptibility gene through GWAS in European patients with type 2 diabetes is significant. Multiple SNPs in the gene's first intron have been linked to type 2 diabetes, but this association disappears when BMI is taken into account. This suggests that FTO's effect on BMI mediates the association between FTO and type 2 diabetes. A study in Sardinian patients confirmed these findings, identifying rs9939609 and rs9930506 SNPs in FTO that are significantly associated with BMI. Other GWAS studies in European populations have also found SNPs in the same chromosomal location. Furthermore, three large studies conducted in Asian populations reported significant associations between FTO SNPs (rs9939609, rs17817449, rs12149832) and BMI.

Follow the link of the selected polymorphism to read a brief description of how the selected polymorphism affects Obesity and see a list of existing studies.

SNP polymorphisms related to the topic Obesity: