It was around this time that American life insurance companies began collecting data on their policyholders. The social and health benefits of appropriate body weight were quickly brought to the public’s attention. The largest life insurance mortality analysis, the “Build and Blood Pressure Studies,” included data on more than 100,000,000 policyholder-years.1 These studies found that the risk of premature mortality increased steadily at all build levels from underweight to overweight. For the first time, there was evidence to suggest that excessive girth was associated with greater mortality rates. Life insurance companies published magazine advertisements and distributed pamphlets encouraging appropriate body weight through proper diet and regular physical exercise. For the first time, people began to pay attention to their weight. Across the nation, millions of healthy persons were weighed at life insurance and medical examinations and as military draftees. Soon, drugstore coin-operated penny scales became the rage, and a few decades later, bathroom scales provided some measure of privacy.
One result of this diet-conscious behavior was a precipitous drop in the consumption of flour and other cereal grains. In the late 19th century, the average American consumed over 300 pounds of breads, cakes, and cereals, but 50 years later, this number was cut in half. An editorial in the Journal of the American Medical Association written in 1948 presciently warned of a potential rise in the prevalence of obesity if this reduction was to be replaced by a heightened consumption of sugars and fats.2 In fact, a mere 20 years later, obesity rates began to climb so that today, the weight breakdown of our population is approximately one-third obese, one-third overweight (defined as having a BMI between 25 and 30), and one-third in the normal range (BMI less than 25).
Why are obesity rates soaring? There are several plausible explanations. First, the industrialization of the American farm, along with the liberal use of pesticides, boosted food production. In 1970, according to the U.S. Department of Agriculture, the food supply provided, on average, 2,086 calories per person per day; by 2010, this amount had risen to 2,534 calories, an increase of more than 20%. Second, the past 40 years have witnessed the spectacular growth of the fast-food industry. High-calorie, tasty snacks, disproportionately sized meals, and sugar-laden beverages can be purchased everywhere. Third, as families transitioned from having single- to dual-income earners, greater time stresses were created. This fostered a heightened demand for fast-food options in place of healthier home-cooked meals. Nowadays, about one-fifth of the daily calories consumed by the average American are derived from sources outside of the home.3
There is mounting evidence to support the concept that obesity represents a form of a low-grade inflammatory state.
The New Frontier in Inflammation: Immunometabolism
Many physicians consider obesity to be either a public health or endocrine issue. If so, should the obesity epidemic matter to rheumatologists? There is mounting evidence to support the concept that obesity represents a form of a low-grade inflammatory state. As tissues become unresponsive to insulin, the pancreas compensates by secreting more insulin, yet these tissues become more resistant.4 In some animal models of obesity, insulin resistance could be induced in vitro by exposing fat cells to tumor necrosis factor (TNF) α. Conversely, obese strains of mice could be protected from insulin resistance by knocking out the genes for either TNF-α or for TNF-α receptors. Large, overstuffed fat cells activate the immune system, promoting elevated levels of inflammatory cytokines including interleukin 6, TNF-α, and JNK. Obesity appears to provide bacterial and metabolic danger signals that drive inflammatory adipose tissue (AT)–resident immune-cell responses. In patients with the metabolic syndrome, estimated to comprise about one-fifth of most rheumatology practices, the overflow of saturated fatty acids can activate endoplasmic reticulum stress-related, TLR-4–mediated, and inflammasome-mediated inflammatory pathways. Downstream, this translates into the ectopic deposition of fatty tissue in the muscles, liver, and other organs. I often wonder whether fatty liver syndrome may be the true culprit for the serum aminotransferase elevations observed in some of my heavier patients who are treated with methotrexate. Although some lipid components such as the “healthy” omega-3 fatty acids exhibit antiinflammatory and insulin sensitizing effects, the predominant effects of lipid spillover in obesity are profoundly inflammatory.5
