At the TOSP, we bridge the gap between research and real-life solutions for obesity. Our study is based on the latest scientific findings, ensuring that our recommendations are credible and effective.
Genetics of Obesity – Identifying genetic factors that increase obesity risk.
Hormonal & Metabolic Studies – Understanding how metabolism and hormones influence weight.
Lifestyle & Environment – Investigating the role of diet, physical activity, and urban living.
Obesity is more than just eating too much and is deeply connected to our genes. Through our research, we have uncovered critical genetic mutations that help explain why some people struggle with severe obesity at an early age. These discoveries are paving the way for new treatments and a better understanding of how our bodies control their body weights. Some of our key findings are as follows:
Key Genetic Findings in Obesity Research
1. Leptin (LEP) and Melanocortin-4 Receptor (MC4R) Mutations: The Hunger Switch
Imagine feeling constantly hungry, no matter how much you eat. This is the reality for people with mutations in the Leptin (LEP), Leptin Receptor (LEPR), and MC4R genes—key regulators of hunger and satiety.
• Leptin Deficiency: Leptin is a hormone that signals the brain when the body is full. Without it, the brain perceives starvation, leading to uncontrolled hunger and rapid weight gain. Our research found that many Pakistani children with severe obesity have genetic leptin deficiency, making early diagnosis and treatment essential. (Source: Saeed et al., 2023, Cell Reports Medicine)
• Leptin Receptor (LEPR) Mutations: When the LEPR gene is mutated, leptin signaling is disrupted, leading to severe obesity, similar to congenital leptin deficiency. 15% of Pakistani children from consanguineous families with early-onset obesity carry LEPR mutations. (Source: Saeed et al., 2020, Diabetes)
• MC4R Mutations: MC4R is a crucial gene for appetite regulation. Individuals with MC4R mutations do not feel full after eating, leading to excessive food intake and obesity. Identifying these mutations has led to targeted treatments, such as MC4R-activating drugs. (Source: Saeed et al., 2012, Molecular Genetics and Metabolism)
One of our most exciting findings is the role of loss-of-function mutations in ADCY3, a gene that controls how the body utilizes energy. When ADCY3 does not function properly, it leads to:
• Rapid weight gain, even with a normal diet.
• Impaired sense of smell, demonstrating how genetic mutations can impact more than just body weight.
This discovery has opened doors for precision medicine, where treatments are customized based on a person’s unique genetic profile. (Source: Saeed et al., 2018, Nature Genetics)
Our research has revealed that mutations in the P4HTM gene cause syndromic obesity, where obesity is accompanied by other medical conditions.
• Children with this mutation not only gain excessive weight but also experience developmental delays and other health issues.
• Identifying this gene allows for earlier diagnosis and management, improving the quality of life for affected individuals.
(Source: Saeed et al., 2023, Diabetes)
Our research on young adults with severe obesity from consanguineous families in Pakistan has uncovered rare pathogenic mutations, reinforcing the genetic basis of early-onset obesity.
(Source: Saeed et al., 2022, Diabetes)
