Persistent effects of obesity: a neuroplasticity hypothesis

Abstract

The obesity epidemic is a leading cause of health problems in the United States, increasing the risk of cardiovascular, endocrine, and psychiatric diseases. Although many people lose weight through changes in diet and lifestyle, keeping the weight off remains a challenge. Here, we discuss a hypothesis that seeks to explain why obesity is so persistent. There is a great degree of overlap in the circuits implicated in substance use disorder and obesity, and neural plasticity of these circuits in response to drugs of abuse is well documented. We hypothesize that obesity is also associated with neural plasticity in these circuits, and this may underlie persistent changes in behavior, energy balance, and body weight. Here, we discuss how obesity-associated reductions in motivation and physical activity may be rooted in neurophysiological alterations in these circuits. Such plasticity may alter how humans and animals use, expend, and store energy, even after weight loss.

Keywords: glutamate; high-fat diet; obesity; plasticity; synaptic.

Figure 1

(A) Schematic showing how obesity induces neural mechanisms that lead to behavioral changes in both humans and rodents. (B) Flowchart of proposed biomolecular changes in the striatum during obesity or after HFD that lead to altered synaptic function. (C) Cartoon illustrating the cyclic nature of obesity. Obese states lead to changes in synaptic plasticity that can persist despite weight loss. This contributes to physiological and behavioral factors contributing to relapse and ultimately the cyclic nature of weight gain and loss.