Physiological Aspects of Obesity

Lecture Overview

This study guide summarizes the physiological and genetic factors underlying obesity, focusing on energy expenditure, adipose tissue anatomy and function, health risks associated with fat distribution, and the genetic basis of body weight regulation.

Energy Expenditure and Energy Balance

Components of Energy Expenditure

Energy expenditure refers to the total amount of energy used by the body, which is crucial for maintaining energy balance and body weight. It is composed of three main components:

• Resting Energy Expenditure (REE): The energy required to maintain vital body functions at rest. This includes the Basal Metabolic Rate (BMR) and Obligatory Thermogenesis.

• Thermic Effect of Food (TEF): The energy expended to digest, absorb, transport, metabolize, and store nutrients after eating (also called post-prandial thermogenesis).

• Energy Spent in Physical Activity: The energy used during both exercise and non-exercise activities (e.g., walking, cleaning). This is the most modifiable component of energy expenditure.

Example: For a typical adult, BMR accounts for about 70% of total daily energy expenditure, physical activity for 20%, and TEF for 10%.

Factors Influencing Resting Energy Expenditure

Several factors affect REE, including:

• Age: REE decreases with age.

• Sex: Males generally have higher REE than females.

• Body Size and Composition: Larger individuals and those with more lean muscle mass have higher REE.

• Hormones: Thyroid hormones, in particular, play a significant role.

Basal Metabolic Rate (BMR): Factors Affecting BMR

BMR is the largest component of energy expenditure. The following table summarizes factors that increase or decrease BMR:

Physical Activity

Physical activity is the second largest contributor to total energy expenditure and is highly variable among individuals (15–30% depending on lifestyle). It includes:

• Non-Exercise Activity Thermogenesis (NEAT): Activities such as walking, cleaning, and stair climbing.

• Exercise Activity Thermogenesis (EAT): Activities such as jogging, yoga, and sports.

Key Point: Physical activity is the most modifiable component of energy expenditure.

Thermic Effect of Food (TEF)

TEF is the smallest contributor to energy expenditure. It represents the energy used to process food after a meal, including:

• Digestion

• Absorption

• Transport

• Metabolism

• Storage

TEF depends on the amount and type of food consumed. High-protein foods have the highest TEF, while high-fat foods have the lowest.

Anatomy and Function of Adipose Tissue

Types of Adipose Tissue

Adipose tissue is a specialized connective tissue involved in energy storage, insulation, and hormone production. There are two main types:

• White Adipose Tissue (WAT): Most abundant, stores energy as triglycerides, and secretes various bioactive substances (adipokines).

• Brown Adipose Tissue (BAT): Less abundant, located in specific regions (e.g., interscapular, supraclavicular), rich in mitochondria, and contributes to adaptive thermogenesis (heat production).

Beige Adipose Tissue: Intermediate characteristics between white and brown adipose tissue. Can be induced under certain conditions (e.g., cold exposure).

Adipose Tissue Distribution

Adipose tissue is distributed in two main compartments:

• Subcutaneous Adipose Tissue: Located under the skin, stores over 80% of total body fat.

• Visceral Adipose Tissue: Surrounds internal organs (e.g., intra-abdominal, perirenal, pericardial). Visceral fat is more strongly associated with metabolic abnormalities and obesity-related health risks.

Differences in Fat Deposition

Fat distribution patterns influence health risks:

• Android (central/abdominal) obesity: More visceral fat, higher risk of metabolic diseases.

• Gynoid (hip/thigh) obesity: More subcutaneous fat, lower risk of metabolic diseases.

Adipose Tissue Remodeling and Health Risks

Adipose Tissue Remodeling

Adipose tissue can expand by increasing the number (hyperplasia) or size (hypertrophy) of adipocytes. The mode of expansion affects health risks:

• Hyperplasia: Increase in cell number; considered more protective.

• Hypertrophy: Increase in cell size; associated with greater risk of inflammation, insulin resistance, and metabolic dysfunction.

Adipokine Production and Dysfunction

Adipocytes secrete adipokines (proteins/hormones) that regulate physiological functions such as appetite, metabolism, and inflammation. In obesity, dysfunctional adipose tissue alters adipokine production, promoting chronic inflammation and metabolic disease.

• Healthy adipose tissue: Produces beneficial adipokines (e.g., adiponectin, omentin-1).

• Dysfunctional adipose tissue: Increases pro-inflammatory adipokines (e.g., resistin, leptin) and decreases protective ones.

Ectopic Fat Deposition

When adipose tissue storage capacity is exceeded, fat accumulates in non-adipose tissues (e.g., liver, pancreas, heart), leading to ectopic fat deposition. This promotes local cell dysfunction, impaired metabolism, and increased risk of diseases such as type 2 diabetes and cardiovascular disease.

Genetic Influences on Obesity

Genetic Heritability of Body Weight

Body weight is highly heritable, with up to 70% of variation between individuals attributed to genetic factors. Twin studies show higher concordance of body weight in monozygotic (identical) twins compared to dizygotic (fraternal) twins, even when raised apart.

Genes and Obesity

• Gene: The basic unit of heredity, composed of DNA, encoding instructions for protein synthesis.

• Humans have over 20,000 genes, with two copies of each gene inherited from each parent.

• Variations in a small subset of genes contribute to individual differences in body weight and fat distribution.

Monogenic Obesity

Rare forms of obesity result from mutations in a single gene (monogenic obesity), often characterized by early-onset, severe obesity and hyperphagia (excessive hunger). An example is congenital leptin deficiency, where mutations in the leptin gene lead to constant hunger and rapid weight gain.

Summary Table: Components of Energy Expenditure

Key Equations

• Energy Balance Equation:

• Basal Metabolic Rate (BMR) (Harris-Benedict Equation, example for men):

• For women:

Home Messages

• Total energy expenditure is determined by BMR, physical activity, and TEF.

• BMR is the largest contributor and is influenced by age, sex, body composition, and hormones.

• White adipose tissue is the most abundant and is distributed into subcutaneous and visceral compartments.

• Adipose tissue remodeling, especially hypertrophy, underlies the severity of obesity-related health risks.

• Genetic factors play a significant role in individual differences in body weight; monogenic obesity is rare but informative.