Why Can’t We Stop Eating?by Nisha Cooch, PhD | April 22, 2014
We have long known the simplest recipe for weight loss: eat less and exercise more. Yet despite our understanding of the causes of weight fluctuation and the serious health risks associated with obesity, our collective weight continues to rise.
Researchers have suggested several potential culprits for the ‘obesity epidemic,’ including genetic predisposition, lack of education, and cultural incentives for unhealthy behaviors (such as time and cost savings). However, none of these factors provides a thorough explanation of the problem. Indeed, most of us, regardless of our specific genes, knowledge, and cultures, can relate to the desire to eat too much, and many of us indulge in this temptation, despite our rational understanding of the disadvantages of doing so.
Though there are likely several factors that lead to obesity, it is generally accepted that the most direct cause for obesity is excessive consumption. Thus, the most universal solution for obesity may intervene in the decision making process by modifying feeding choices. A prerequisite for such a solution is an understanding of the neural mechanisms underlying our decisions regarding food.
In response to the complexity of obesity and to the recent controversial declaration by the American Medical Association (AMA) that obesity is itself a disease, Nature featured a comprehensive Outlook issue on the ‘disease’ this month. The collection of articles closed with a discussion of the neural circuits involved in appetite, the elucidation of which has been greatly facilitated in the past few years by the development of optogenetic techniques, which allow for the activation and inactivation of individual neurons using light.
According to Bradford Lowell, a neuroscientist at Beth Israel Deaconess Medical Center in Boston, the hypothalamus, which has long been recognized as the feeding center of the brain, is “a tangle of circuits that look like a Jackson Pollock painting.” The Nature discussion on the physiology of appetite included an explanation of agouti-related peptide (AgRP) neurons and pro-opiomelanocortin (POMC) neurons in the hypothalamus, which stimulate and suppress appetite, respectively. In the 1990s, scientists demonstrated that knocking out the genes for individual appetite stimulator peptides does not affect eating behavior or weight. Further, though full destruction of the AgRP nucleus in mice results in starvation, GABA receptor stimulation of the parabrachial nucleus, which communicates directly with the hypothalamus, reinstates food consumption. It thus appears that mammals have evolved some neural redundancy that increases the chances that we remember to eat.
Nonetheless, the circuitry underlying appetite can be altered such that eating becomes excessive or absent. For example, loss of oxytocin neurons in the hypothalamus produces an insatiable appetite, as observed in Prader-Willi syndrome, whereas stimulation of calcitonin gene-related protein (CGRP) neurons in the parabrachial nucleus of mice leads to starvation. The latter examples illustrates one challenge in dealing with obesity: unlike with drugs of abuse, abstinence from food is not a viable solution to problematic indulgence.
Some researchers believe that our understanding of the molecules that signal hunger and satiety information will facilitate the development of drugs that are effective for eating disorders. However, I believe there are limitations to this approach. First, the sensation of hunger often indicates a physiological need. We can consume many (‘empty’) calories without satiety if the calories do not consist of appropriate amounts of protein. Thus, pharmacologically blocking hunger or inducing satiety may prevent consumption of important nutrients and exacerbate health problems. Second, much of our problematic eating is not actually a response to hunger. In other words, we often eat not to eliminate the aversive sense of hunger, but to reap the rewarding effects of food that are independent of nourishment. Enhancing satiety would likely have little impact on this type of consumption.
Though the integration of reward signals in the hypothalamus is mentioned in the Outlook issue of Nature, the implications of the rewarding effects of food consumption are largely ignored. Nonetheless, the impact of high sugar and high fat foods on reward centers of the brain is reminiscent of that of drugs of abuse. Like drugs, these foods enhance dopamine release in the midbrain, thereby increasing the likelihood that such foods will be consumed again in the future. Drug addicts and compulsive eaters also both display structural abnormalities in the prefrontal cortex (PFC), which is important for executive control. Accordingly, both populations tend to have difficulty controlling their consumption, despite the negative consequences associated with it. Such behavior is consistent with the abundance of research suggesting that changes in PFC render us more vulnerable to reward and habitual behaviors and that those with such changes tend to choose immediate gratification over long-term accomplishments.
Much of society’s food consumption results from reward signals that are not nutritionally informative. Further, behaviors resulting from these reward signals reinforce unhealthy choices. Targeting these signals, rather than hypothalamic signals that indicate nutritional status, may therefore be more effective in reducing problematic eating and promoting overall health.
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