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Chapter 394: Pathobiology of Obesity

Jeffrey S. Flier; Eleftheria Maratos-Flier

INTRODUCTION

In a world where food supplies are intermittent, the ability to store energy in excess of what is required for immediate use is essential for survival. Fat cells, residing within widely distributed adipose tissue depots, are adapted to store excess energy efficiently as triglyceride and, when needed, to release stored energy as free fatty acids for use at other sites. This physiologic system, orchestrated through endocrine and neural pathways, permits humans to survive starvation for as long as several months. However, in the presence of nutritional abundance and a sedentary lifestyle, and influenced importantly by genetic endowment, this system increases adipose energy stores and produces adverse health consequences.

DEFINITION AND MEASUREMENT

Obesity is a state of excess adipose tissue mass. Although often viewed as equivalent to increased body weight, this need not be the case—lean but very muscular individuals may be overweight by numerical standards without having increased adiposity. Body weights are distributed continuously in populations, so that choice of a medically meaningful distinction between lean and obese is somewhat arbitrary. Obesity is therefore defined by assessing its linkage to morbidity or mortality.

Although not a direct measure of adiposity, the most widely used method to gauge obesity is the body mass index (BMI), which is equal to weight/height² (in kg/m²) (Fig. 394-1). Other approaches to quantifying obesity include anthropometry (skinfold thickness), densitometry (underwater weighing), computed tomography (CT) or magnetic resonance imaging (MRI), and electrical impedance. Using data from the Metropolitan Life Tables, BMIs for the midpoint of all heights and frames among both men and women range from 19 to 26 kg/m²; at a similar BMI, women have more body fat than men. Based on data of substantial morbidity, a BMI of 30 is most commonly used as a threshold for obesity in both men and women. Most but not all large-scale epidemiologic studies suggest that all-cause, metabolic, cancer, and cardiovascular morbidity begin to rise (albeit at a slow rate) when BMIs are ≥25. Most authorities use the term overweight (rather than obese) to describe individuals with BMIs between 25 and 30. A BMI between 25 and 30 should be viewed as medically significant and worthy of therapeutic intervention in the presence of risk factors that are influenced by adiposity, such as hypertension and glucose intolerance.

FIGURE 394-1

Nomogram for determining body mass index. To use this nomogram, place a ruler or other straight edge between the body weight (without clothes) in kilograms or pounds located on the left-hand line and the height (without shoes) in centimeters or inches located on the right-hand line. The body mass index is read from the middle of the scale and is in metric units. (Copyright 1979, George A. Bray, MD; used with permission.)