Monogenic obesity refers to obesity resulting from mutations in a single gene. It is less common than polygenic obesity, which involves variations in multiple genes and is influenced by environmental factors. Monogenic obesity typically manifests early in life and can lead to severe obesity and often, resistance to traditional weight loss methods, including diet and exercise. Here are some examples of genes involved in monogenic obesity:
1. Leptin (LEP) Gene Mutations: Leptin is a hormone produced by fat cells. It regulates energy balance by inhibiting hunger, which in turn diminishes fat storage in adipocytes. Mutations in the LEP gene can lead to a lack of leptin, resulting in severe early-onset obesity and intense hunger.
2. Leptin Receptor (LEPR) Gene Mutations: The LEPR gene encodes the leptin receptor, which is necessary for the normal function of leptin. Mutations in this gene can lead to leptin resistance, causing severe obesity due to the inability to regulate appetite and energy expenditure effectively.
3. Melanocortin 4 Receptor (MC4R) Gene Mutations: The MC4R gene mutations are among the most common causes of monogenic obesity. The MC4R gene encodes a receptor involved in regulating appetite and energy balance. Mutations can lead to an increased appetite and reduced energy expenditure.
4. Pro-opiomelanocortin (POMC) Gene Mutations: POMC is a precursor peptide that gets cleaved into several active hormones, including those that impact appetite and satiety signals in the brain. Mutations in the POMC gene can lead to early-onset obesity due to disrupted signaling pathways.
5. Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1) Gene Mutations: PCSK1 is involved in the processing of prohormones, including POMC. Mutations can affect the appetite-regulating effects of POMC, resulting in early-onset obesity and sometimes endocrine problems.
6. Single-minded family BHLH transcription factor 1 (SIM1) Gene Mutations: SIM1 gene mutations can lead to obesity by affecting the development and function of the hypothalamus, the brain region responsible for regulating hunger and satiety.
These genetic mutations are often identified through genetic testing when there is a history of early-onset obesity that does not respond to standard treatment methods. Understanding the genetic underpinnings of obesity can help tailor treatment and management options for affected individuals, including possible hormone replacement therapies (e.g., leptin therapy in leptin-deficient individuals) or targeted medications.
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