Obesity Medicine

Pathophysiology of Obesity

The pathophysiology of obesity refers to the complex biological processes that lead to excessive fat accumulation and the development of obesity. This condition arises from an imbalance between energy intake and energy expenditure, but the underlying mechanisms are influenced by multiple factors, including genetics, hormones, metabolic pathways, and environmental triggers.

Key Factors in Obesity Pathophysiology:

1. Genetic and Epigenetic Factors:

   • Obesity has a strong genetic component, with certain gene variants linked to increased appetite, reduced energy expenditure, and fat storage. Epigenetic modifications, influenced by diet, environment, and lifestyle, can also affect how genes related to obesity are expressed.

2. Hormonal Regulation and Appetite Control:

   • Hormones like leptin (which signals satiety) and ghrelin (which stimulates hunger) play key roles in regulating energy balance. In individuals with obesity, leptin resistance often occurs, reducing the effectiveness of this hormone in controlling appetite, leading to overeating and weight gain.

3. Metabolic Dysregulation:

   • Obesity is associated with disruptions in normal metabolic processes, including insulin resistance, which contributes to the development of type 2 diabetes. In obesity, excess fat, especially in visceral areas, alters the function of adipose tissue, increasing inflammation and impairing normal glucose and lipid metabolism.

4. Gut Microbiota:

   • The gut microbiome, a community of microorganisms in the digestive tract, plays a role in nutrient absorption and metabolism. Changes in gut microbiota composition have been linked to obesity, influencing energy harvest from food and promoting fat storage.

5. Inflammation and Adipose Tissue Dysfunction:

   • In obesity, adipose (fat) tissue becomes enlarged and dysfunctional, leading to increased secretion of pro-inflammatory cytokines. Chronic, low-grade inflammation in obesity contributes to the development of metabolic disorders like insulin resistance, hypertension, and cardiovascular disease.

6. Neuroendocrine Dysregulation:

   • The hypothalamus, a region of the brain involved in regulating hunger and energy balance, may become dysregulated in obesity. Changes in neural pathways that control feeding behaviors and energy expenditure can lead to excessive calorie intake and reduced physical activity.