Food reward, hyperphagia, and obesity

Abstract

Given the unabated obesity problem, there is increasing appreciation of expressions like "my eyes are bigger than my stomach," and recent studies in rodents and humans suggest that dysregulated brain reward pathways may be contributing not only to drug addiction but also to increased intake of palatable foods and ultimately obesity. After describing recent progress in revealing the neural pathways and mechanisms underlying food reward and the attribution of incentive salience by internal state signals, we analyze the potentially circular relationship between palatable food intake, hyperphagia, and obesity. Are there preexisting individual differences in reward functions at an early age, and could they be responsible for development of obesity later in life? Does repeated exposure to palatable foods set off a cascade of sensitization as in drug and alcohol addiction? Are reward functions altered by secondary effects of the obese state, such as increased signaling through inflammatory, oxidative, and mitochondrial stress pathways? Answering these questions will significantly impact prevention and treatment of obesity and its ensuing comorbidities as well as eating disorders and drug and alcohol addiction.

Fig. 1.

Schematic flow diagram showing the relationship between the classical homeostatic regulator (dark gray boxes) and neural systems involved in reward, cognitive, and executive functions (light gray boxes). Note that humoral (broken lines with open arrows) and neural (full lines with open arrows) signals from peripheral organs handling energy assimilation and metabolism not only feed back to the hypothalamus and brainstem, but also to sensory and corticolimbic structures. Similarly, effector pathways can be accessed not only from hypothalamus and brainstem, but also from a number of corticolimbic structures (broken lines with closed arrows).

Fig. 2.

Relationship between metabolic and hedonic controls of food intake and energy balance. The metabolic consequences of food are regulated by homeostatic functions and the hedonic consequences by reward functions. Hedonic and metabolic consequences are interdependent in that the hedonic value of food modulates caloric intake (1), and the metabolic status modulates hedonic processing (2). The obese state is associated with altered reward functions, but it is not clear whether these changes are the cause or consequence of obesity. Altered reward functions could cause obesity via increased intake of calories or fat (1), or alternatively, could result from consequences of the obese state (3), or could be a combination of both.

Fig. 3.

Conceptual representation of mechanisms in palatable food-induced hyperphagia. An environment of plenty favors habitual intake of palatable foods that can accelerate to an addiction-like state when normal reward processing is corrupted by hyperactivity and/or neurotoxic effects of obesity. Reinstatement of inhibitory controls and/or a change in environment can result in abstinence.

Fig. 4.

Secondary effects of obesity on reward circuitry and hypothalamic energy balance regulation. Palatable and high-fat diets can lead to obesity with or without hyperphagia. Increased inflammatory, mitochondrial, and oxidative stress signaling within the brain leads to neural/microglial alterations impinging on the hypothalamus and corticolimbic systems involved in reward functions, accelerating the development of obesity.