From Energy Equation Proposes Patterns of Weight Gain and Loss in FOCUS Online, the e-journal of the Harvard medical schools:
The model predicts that mice susceptible to developing resistance to the metabolic regulator leptin have multiple stable body weights. Simulated mice based on the model grow obese after overeating, eventually hitting a high stable weight. But losing this weight and returning to a lower stable weight can be extraordinarily difficult. Though the model blends two competing theories of body weight, it departs from their predictions that body weight gravitates to one stable weight or weight range. If the model proves correct, it may point to new interventions to help ease weight loss even in the most intractable cases.That's what happens when you let Engineers do medicine in a cross-discipline environment. You have to translate their words into a more usual form, but they come up with plausible, imaginative, neat and even just possibly correct answers to intractable problems.
Simulated mice representing the set point model never remained obese; their weights always returned to the set point. This contradicted evidence of diet-induced obesity in live mice. The settling point model contradicted evidence in the case of starvation.
So Tam decided to combine the two models. The unified model uses the set point theory to simulate the case of starvation, but when leptin levels in the brain cross a certain threshold, the settling point dynamics take over. This kind of combination, said Jain, is very common in thermodynamics. “You develop it based on one phase, then another phase, then you mix it together.”
It is not, however, common in biology. Co-author Dai Fukumura, HMS associate professor of radiation oncology at MGH, played a large role in this work by acting as a translator. He helped Tam and Jain ground their model in biology and also helped them change their engineering-centric (and, to them, “common sense”) explanations into more accessible terms.
Another element Tam added to the models was a way to simulate leptin resistance. Leptin is a hormone produced by fat tissue. It crosses the blood–brain barrier and signals the body to stop eating. In its absence, the body craves food. A decreased sensitivity to leptin results in unnecessarily high food intake, so it is thought to be a cause of diet-induced obesity. It is also thought to be a consequence of obesity because, as fat stores increase, leptin concentrations also increase, eventually triggering the development of resistance.