Hypothalamic regulation of obesity

Abstract

Obesity has now reached pandemic proportions and represents a major socioeconomic and health problem in our societies. Up to now, obesity has been considered a medical issue only in high-income countries, but this disease is now dramatically on the rise in low- and middle-income countries, particularly in urban settings, affecting both adults and the pediatric population [1]. The simplest definition of overweight and obesity is an excessive accumulation of fat due to an imbalance between the energy in and the energy out, and this adiposity represents a risk to health [1]. But the whole picture is more complex than this, and obesity is a marker of a serious metabolic dysregulation that involves several diseases such as type 2 diabetes, cancer, cardiovascular pathologies, and most recently for COVID-19 infection [1,2]. Since the current approaches to combatting obesity and its complications have limited clinical effectiveness, gaining insight into the cellular and molecular basis of obesity could lay the foundations for the development of new strategies to prevent metabolic disruption and to treat this somewhat unaddressed medical issue. In the last few decades, it has been strongly demonstrated that the hypothalamus is the master regulator of energy homeostasis. The hypothalamus contains hormone- and nutrient-sensing nuclei that organize central and peripheral responses for maintaining normal body weight, food intake, energy expenditure, and nutrient partitioning. Within the hypothalamus, specialized sub-populations of neurons are connected to each other and to various extrahypothalamic regions to coordinate energy balance. Evidence has also highlighted the participation of non-neuronal populations (i.e., microglia and astrocytes), and even the interesting cross-talk between these types of brain cells, whose disruption leads to insulin resistance and obesity. In this Special Issue, we report on the most recent insights into the hypothalamic circuitries and pathways involving neurons [3,4,5,6,7], astrocytes [8,9], and microglia [10,11] in obesity development and associated complications. The emerging contribution of astrocyte–neuron [9] and microglia–neuron cross-talks [12] in the hypothalamus and the contribution of microbiota and the gut-brain axis controlling food intake and energy homeostasis [13] are also presented in this Special Issue.