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.
