Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction
Common Cellular and Molecular Mechanisms in Obesity and Drug Addiction
Is Fast Food Addictive?
Metabolic and Hedonic Drives in the Neural Control of Appetite: Who is the Boss?
The truth of the matter is, obesity researchers have been converging on the food reward hypothesis for years now-- and I'm a relative latecomer. I recently came across an outstanding 2008 review paper by several leaders in the field titled "Mechanisms of Leptin Action and Leptin resistance" (1). I highly recommend this review to anyone with a background in the biological sciences who wants to understand how leptin works in both the lean and obese state. Here's a passage from the end of the paper:
Some evidence exists for developmental alterations in neural and other systems that may underlie some propensity to obesity, but the ready availability of palatable, calorically dense food (the basis for [diet-induced obesity] in experimental animals) clearly plays a dominant role. Indeed, the obesity and cellular leptin resistance of [diet-induced obese] animals are reversed by replacing the palatable calorie-dense chow used to promote obesity with standard chow. Although some of the obesogenic effects of tasty foods may be due to their nutrient content, the hedonic or rewarding properties of these foods also contribute...
How then is the action of leptin to regulate the perception of food reward overwhelmed to promote obesity in the face of plentiful tasty food? Leptin is only one of many inputs into the mesolimbic [dopamine] system and other neural pathways that regulate the perception of food reward, and physiological leptin levels may not be able to suppress the myriad other signals that compel us to consume tasty food. Although leptin may reasonably inhibit the drive to overeat foods with only modestly rewarding properties, leptin may be insufficient to effectively compete with the rewarding properties of more palatable treats because these more-rewarding foods engage powerful neural responses that oppose leptin within the mesolimbic [dopamine] system and elsewhere.Basically, what they're saying is pretty simple: the brain's hard-wired mechanisms for regulating food intake and fat mass in a natural environment are not sufficient to protect against modern hyper-palatable and hyper-rewarding food. These are researchers who primarily study the mechanisms of leptin resistance in the brain. If anything, they have an incentive to de-emphasize the food reward hypothesis as it potentially takes the spotlight off their own research (the same applies to me). The fact that they nevertheless place such a strong emphasis on the idea speaks volumes.
The journal Cell just published a review paper by Drs. Karen Ryan, Randy Seeley and Stephen Woods-- Drs. Seeley and Woods are leaders in obesity research (2). Here's what they had to say about food reward:
When a [high-fat diet] is suddenly made available to an individual, sensory properties of the food (e.g., odor, taste, mouth feel) are intrinsically pleasant and lead to more food being consumed. As this continues, excess calories accumulate as increased adiposity, and increased circulating fatty acids lead to increased lipid flux into the brain, insulin/leptin resistance, an inflammatory condition, and so on. Stated another way, the increased palatability of the diet initiates a vicious cycle in which hedonics cause more food to be eaten than is necessary to meet energy needs, and the increased calories in turn initiate events that lead to insulin/leptin resistance and a consequent tendency to eat even more food (Figure 4).It's worth noting that they're referring specifically to insulin and leptin resistance in the brain in that passage. I do differ with them somewhat on the role of fat per se.
Dr. Robert Lustig just published an editorial in the journal Nature titled "Public Health: the Toxic Truth About Fructose" (3). First of all, congratulations to Dr. Lustig for publishing his letter in such a high-impact journal. He argues that sugar consumption should be regulated by the government because in excess, it's a threat to public health. One section of the article describes sugar's effects on the reward and pleasure systems in the brain:
Sugar also has clear potential for abuse. Like tobacco and alcohol, it acts on the brain to encourage subsequent intake. There are now numerous studies examining the dependence-producing properties of sugar in humans6. Specifically, sugar dampens the suppression of the hormone ghrelin, which signals hunger to the brain. It also interferes with the normal transport and signalling of the hormone leptin, which helps to produce the feeling of satiety. And it reduces dopamine signalling in the brain's reward centre, thereby decreasing the pleasure derived from food and compelling the individual to consume more1, 6.Another nice food reward review paper (4), hot off the presses, had this to say:
Food reward, not hunger, is the main driving force behind eating in the modern obesogenic [obesity-promoting] environment. Palatable foods, generally calorie-dense and rich in sugar/fat, are thus readily overconsumed despite the resulting health consequences.Last but not least, my own recent review paper on obesity, published in the Journal of Clinical Endocrinology and Metabolism (5). I don't claim to be a leader in the obesity research field, but my mentor Dr. Michael W. Schwartz, senior author on the paper, is. Here's what we had to say:
These findings collectively suggest that obesity can arise when animals or humans are confronted with foods whose palatability/reward value greatly exceeds that to which they are genetically adapted, and hence that interventions that inhibit food reward can prevent fat gain and promote fat loss.These latter four review papers were all published in the last couple of months.
Approaching a Consensus
There are many different research groups approaching obesity from many different angles, but most of the review papers being published today acknowledge the central role of food reward in the development of obesity. The reason is simple: the idea is strongly supported by the scientific literature, but it's also just common sense. In any scientific discipline, there will always be some disagreement, but the evidence at this point is strong enough that the field as a whole seems to be reaching a consensus.
* Reward. The brain contains a "reward" system, whose job it is to gauge the desirability of food (among other things) and reinforce and motivate behaviors that favor the acquisition of desirable food. For example, if you eat a strong cheese for the first time, maybe it won't taste very good to you. As it's digested, your reward system gets wind that it's full of calories however, and the next few times you eat it, it tastes better and better until you like the flavor. This is called an acquired taste, and the reward system is what does the acquiring, motivating you to obtain a food it has deemed safe and desirable. Eventually, you may go out of your way to purchase the cheese or beer at the grocery store because you like it so much, and maybe you'll consume cheese or beer even if you aren't hungry or thirsty. This is an example of the reward system reinforcing and motivating behaviors related to foods that it considers desirable. Processed "junk foods" such as ice cream, fast food, sweetened soda, cookies, cake, candy and deep fried foods are all archetypal hyper-rewarding foods.
Palatability is a related concept-- it is simply the pleasantness of a food; how much a person enjoys eating it. Palatability is determined in part by inborn preferences (e.g., a taste for sugar and energy dense foods), and in part by the reward system (acquired tastes). Palatability is governed by the hedonic system in the brain, which is closely integrated with the reward system.
The reward system is what motivates you to get food and put it to your lips, every time you eat. When scientists shut it down in mice, they completely cease eating (6). The hedonic system influences how much you eat once you begin a meal-- highly palatable food generally increases food intake by activating this system (7). Together, reward and hedonic circuitry in the brain determine in large part how often you eat, what you eat, and how much you eat, and this is influenced by the attributes of the food that's available.