Rheuminations: Why the Obesity Epidemic Should Matter to Rheumatologists

Simon M. Helfgott, MD

Govern well thy appetite, lest sin surprise thee, and her black attendant Death.
—John Milton, Paradise Lost (1667)

To lengthen thy life, lessen thy meals.
—Benjamin Franklin, Poor Richard’s Almanack (1737)

Every four months, I set aside a special time for one of my patients whose visits create a logistical nightmare. Hobbled by a pair of osteoarthritic knees and a body mass index (BMI) well into the upper fifties, Molly barely walks. Not happily, she moved to an assisted living facility at a relatively young age. Her daughter is left with the unenviable task of coordinating her outings. First, she needs to book time off work so that she can accompany her mom to the clinic. Then she reserves a specialized transit car equipped with an oversized wheelchair ramp for the ride to the clinic. When she arrives, we stack my office chairs and shove my desk into a corner. Since Molly and her wheelchair don’t fit easily through the door, she often ends up sitting half in and half out of my office. Scheduling Molly as my last appointment of the day provides her with some faint measure of privacy.

I can’t blame the architects who designed our clinic space 25 years ago for failing to realize that one day, there would be a need for wider doorways that could accommodate wheelchairs ferrying patients who weigh more than 400 pounds. There is a host of other shortsighted design elements in hospitals built in that era. Exam tables are often too narrow, blood pressure cuffs too tight, scales too fragile, ambulance stretchers too flimsy, and imaging equipment too cramped to handle our obese patients (defined as adults having a BMI above 30). Literally, some patients are just too large to fit into our cramped hospital environs. When did this size transformation occur?

Fads, Fat, and Fashion

Actually, the worldwide obesity epidemic is a relatively recent phenomenon. Though many observers consider its onset to be in the early 20th century when the industrialization and modernization of many countries took hold, obesity rates in the United States did not immediately rise. In fact, just the opposite occurred. According to William Rothstein, PhD, professor of sociology at the University of Maryland in Baltimore, a revolution in women’s fashions about 1910 emphasized the “natural figure” and made the slender young woman rather than the full-figured mature body the sought-after model for fashion.¹ The recently designed safety razor encouraged men to shave their beards, and newly exposed double chins were viewed with embarrassment. The wildly popular motion pictures popularized these fashion transformations by depicting willowy women and lanky men. With newer forms of transportation including trucks and railroads, fresh food became more readily available on a year-round basis. Food canning techniques and commercial refrigeration helped to extend the shelf life of fruits and vegetables.

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

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

Can this immune metabolic link be viewed from an evolutionary perspective? Is there a biological benefit to being obese? The answer may lie in our response to infection. Bacterial infections create an acute bioenergetics demand because macrophages and T cells require circulating nutrients for an effective Th1 response and bacterial clearance. The Th1 response in AT may serve to fuel the activated immune system by promoting inflammation and insulin resistance, leading to the mobilization of nutrients via gluconeogenesis, hyperglycemia, and lipolysis.⁶ For most parasitic infections, however, depriving parasites of circulating nutrients is required to slow down parasite growth. Accordingly, the Th2 response in AT prevents inflammation and insulin resistance, and may serve to sequester nutrients for the host. Taken together, this energy-on-demand model presents the Th1 and Th2 responses in AT as an adaptive strategy enabling a tailored immune response against bacteria and parasites while generating deleterious effects for the host.⁷

Manipulating Rheumatic Disease Via Caloric Restriction

If obesity enhances inflammation, does starvation have the opposite effect? Calorie restriction remains the only dietary manipulation known to extend the lifespan of many organisms, including yeast, worms, flies, rodents, and perhaps nonhuman primates. In addition, it has been shown to reduce the incidence of age-related disorders, including diabetes, cancer, and cardiovascular disease in mammals.⁸

We know from the bedside that when caloric intake is severely restricted, patients become anergic. Simply stated, a starving immune system must conserve energy. Before the advent of corticosteroid therapy, starvation was used to treat clinically active lupus. How might it work at the molecular level? During fasting, there is a dramatic reduction in the circulating levels of leptin, an adipokine with proinflammatory effects. A recent study of a murine model of lupus demonstrated that leptin inhibits regulatory T cells, which are important drivers of peripheral immune tolerance.⁹ Regardless of the data, starvation therapy is unlikely to draw many adherents. Might there be more palatable measures to effectively reduce the burden of obesity-related inflammation?

Don’t Eat with Your Eyes

Joseph Delboeuf was a prolific 19th century Belgian scholar whose work in the fields of psychology and mathematics was highly respected. In 1865, he documented a puzzling illusion. Our brains can perceive a difference in the size of two identical circles when a much larger circle surrounds one, while only a slightly larger circle surrounds the other. Take a stroll down the aisles of any Pottery Barn store to see how dinnerware designers put this curious illusion to great use. A series of clever experiments led by Brian Wansink PhD, professor of consumer behavior at Cornell University in Ithaca, NY, have shown that dinner plate size and color can significantly impact the amount of food that we consume. In one study, students were asked to serve the same diameter of soup (a black spot in the center of a Delboeuf diagram) onto dinner plates of varying sizes (the outer circles of these diagrams). The researchers demonstrated that the amount of soup that was served was determined by the relative gap between the edge of the food and the edge of the dinner plate. In other words, the bigger the plate, the more soup was served.10 The students repeatedly overserved into the larger dishes and underserved into the smaller ones, and were quite unaware of their errors. These results have been replicated in other experiments. For example, children at a summer camp were found to eat less cereal when they were provided with smaller bowls.

Since the average size of a dinner plate has grown by almost one-quarter over the past century, it is not surprising that controlling portions can be a daunting challenge. Perhaps the most prominent proponent of portion control has been the former mayor of New York City, Michael Bloomberg. Using his mayoral pulpit and his pocketbook, Bloomberg has worked to improve public health on many fronts. Thanks to his efforts, smoking was outlawed in public places in New York City, trans fats were banned from most menus, and calorie counts are now routinely displayed. However, the courts struck down his proposed ban of the sale of sugary drink servings larger than 16 ounces. They opined that the ban was “arbitrary and capricious.” Though many critics viewed Bloomberg’s public health efforts as a form of meddling in the private lives of citizens, his efforts should be applauded. As a society, we are failing miserably at curbing our calories, and some imposed discipline might not be such a bad idea!

If Mayor Bloomberg cannot succeed in getting us to consume wisely, can peer pressure triumph? Using the cohort of the original Framingham Heart Study and their families, researchers at Harvard Medical School in Boston performed a quantitative analysis of the nature and extent of the person-to-person spread of obesity as a possible factor contributing to the obesity epidemic.11 Their extraordinary findings suggest that obesity may actually spread in social networks in a quantifiable and discernable pattern that depends on the nature of social ties. They found that social distance appears to be more important than geographic distance within these networks. Spouses, who share much of their physical environment, may not affect each other’s weight gain as much as mutual friends do. Pairs of friends and siblings of the same sex appeared to have more influence on the weight gain of each other than did pairs of friends and siblings of the opposite sex. This study also provides support for the social nature of the induction of obesity, since it seems likely that people are more likely to be influenced by those whom they resemble than by those they do not. However, this observation contrasts with the findings of a recent study of twin mice that were discordant for obesity. In this study, fecal transfers from the thin to the obese sib helped to reduce the latter’s weight.12 Mayor Bloomberg, are you listening?

Dr. Helfgott is physician editor of The Rheumatologist and associate professor of medicine in the division of rheumatology, immunology, and allergy at Harvard Medical School in Boston.

References

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