Obesity: pathophysiology and intervention

Abstract

Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity.

Figure 1

Brain circuits related to obesity. The circuits include motivation-drive (e.g., OFC), reward-saliency (e.g., VTA and NAc), inhibitory-control (e.g., DLPFC, ACC, and VMPFC) and learning-memory (e.g., AMY, HIPP, and Putamen). Gray dotted lines represent functional interactions between the brain circuits. In this model, during exposure to the reinforcer (i.e., foods) or to the cues conditioned to the reinforcer, there appears to be an obesity-related lower perception of reward (processed by the learning-memory circuit), which promotes overactivation of the reward-saliency and motivation-drive circuits while decreasing the inhibitory-control circuit activity. The overall outcome in obese persons is a lessened ability or an inability to inhibit the drive to seek and consume foods.