Pathophysiology of obesity
Overview
The pathophysiology of obesity involves complex interactions between genetic, environmental, and physiological factors that lead to an imbalance between energy intake and energy expenditure. Obesity is characterized by an excessive accumulation of body fat and is associated with numerous health complications, including type 2 diabetes, cardiovascular disease, and metabolic syndrome.
Energy Balance and Regulation
The regulation of body weight is primarily governed by the balance between caloric intake and energy expenditure. This balance is influenced by several factors, including:
- Hormonal Regulation: Hormones such as leptin, insulin, and ghrelin play crucial roles in appetite regulation and energy homeostasis. Leptin, produced by adipose tissue, signals the brain to reduce appetite and increase energy expenditure.
- Neural Mechanisms: The hypothalamus is a critical brain region involved in the regulation of hunger and satiety. It integrates signals from hormones and nutrients to maintain energy balance.
- Genetic Factors: Genetic predisposition can influence body weight by affecting metabolic rate, fat storage, and appetite.
Adipose Tissue and Inflammation
Adipose tissue is not merely a passive storage site for fat but an active endocrine organ that secretes various cytokines and hormones, collectively known as adipokines. In obesity, there is an increase in the size and number of adipocytes, leading to:
- Chronic Inflammation: Obesity is associated with a state of low-grade chronic inflammation, characterized by increased levels of inflammatory markers such as C-reactive protein and interleukin-6.
- Insulin Resistance: The inflammatory state contributes to the development of insulin resistance, a key feature of type 2 diabetes.
Metabolic Dysregulation
Obesity is often accompanied by metabolic dysregulation, which includes:
- Dyslipidemia: Elevated levels of triglycerides and low-density lipoprotein (LDL) cholesterol, along with decreased high-density lipoprotein (HDL) cholesterol.
- Hypertension: Increased blood pressure is commonly observed in individuals with obesity, contributing to cardiovascular risk.
- Glucose Intolerance: Impaired glucose metabolism is a precursor to type 2 diabetes.
Environmental and Lifestyle Factors
While genetic factors play a role, environmental and lifestyle factors are significant contributors to the development of obesity. These include:
- Dietary Habits: High-calorie diets rich in sugars and fats contribute to excessive caloric intake.
- Physical Inactivity: Sedentary lifestyles reduce energy expenditure, promoting weight gain.
- Socioeconomic Factors: Access to healthy foods and opportunities for physical activity can be limited by socioeconomic status.
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Contributors: Prab R. Tumpati, MD