Obesity: Peripheral Signals, Neural and Peptidergic

Abstract

Obesity is a global public health problem linked to increased risk for many disorders including diabetes, cardiovascular disease, and even cancer. The World Health Organization estimates almost two billion adults worldwide are considered overweight with nearly 600 million of those individuals also being considered obese. How did we get here? The laws of thermodynamics would suggest it is simply a fact that we consume too many calories without burning an equal number, thus causing an imbalance that results in weight gain and eventual obesity. Such a situation would thus be easy to address, since simply reducing caloric intake would eliminate the problem. However, the story is far more complex and involves the interplay between both central and peripheral systems that regulate energy metabolism, energy consumption, and even the brain’s reward circuitry. This chapter will explore the peripheral signals that not only contribute to obesity but also make it difficult for us to break the cycle that leads to metabolic dysregulation and obesity. We will specifically consider obesity in the context of the brain, which coordinates feeding, activity, circadian rhythms, and metabolic functions, while also being a target for many metabolic hormones. Thus, the state of being obese leads to changes not only in the periphery but also centrally within the brain. How this affects brain structure and function will also be discussed.