Hypothalamic Dysfunction in Obesity and Metabolic Disorders

Abstract

The hypothalamus is the brain region responsible for the maintenance of energetic homeostasis. The regulation of this process arises from the ability of the hypothalamus to orchestrate complex physiological responses such as food intake and energy expenditure, circadian rhythm, stress response, and fertility. Metabolic alterations such as obesity can compromise these hypothalamic regulatory functions. Alterations in circadian rhythm, stress response, and fertility further contribute to aggravate the metabolic dysfunction of obesity and contribute to the development of chronic disorders such as depression and infertility.At cellular level, obesity caused by overnutrition can damage the hypothalamus promoting inflammation and impairing hypothalamic neurogenesis. Furthermore, hypothalamic neurons suffer apoptosis and impairment in synaptic plasticity that can compromise the proper functioning of the hypothalamus. Several factors contribute to these phenomena such as ER stress, oxidative stress, and impairments in autophagy. All these observations occur at the same time and it is still difficult to discern whether inflammatory processes are the main drivers of these cellular dysfunctions or if the hypothalamic hormone resistance (insulin, leptin, and ghrelin) can be pinpointed as the source of several of these events.Understanding the mechanisms that underlie the pathophysiology of obesity in the hypothalamus is crucial for the development of strategies that can prevent or attenuate the deleterious effects of obesity.

Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus

“…The hypothalamus is essential for homeostasis and energy metabolism 2 , 4 , and defects in its development lead to diseases or disorders in adulthood, such as energy imbalance, obesity, anxiety, etc. 7 – 11 .…”

Preventive and Therapeutic Effects of Astaxanthin on Depressive-Like Behaviors in High-Fat Diet and Streptozotocin-Treated Rats

“…Rates of depression are significantly enhanced in diabetic patients: near 20-30% of diabetes patients suffered from clinically relevant depressive disorders (Fiore et al, 2015), and the risk of depression remains elevated over time in some type 2 diabetes patients (Whitworth et al, 2017). The metabolic dysfunction of obesity contributes to the development of depression (Carmo-Silva and Cavadas, 2017), and the interaction between depressive symptoms and metabolic dysfunction may be a risk factor for type 2 diabetes (Schmitz et al, 2016). Alteration in monoamines (serotonin and noradrenaline), increasing cortisol levels and decreasing levels of brain-derived neurotrophic factor (BDNF), could explain the association between depression and diabetes in some of the abnormalities documented in diabetic patients and animal models (Oladeji and Gureje, 2013;Lenart et al, 2016).…”

Predictors of Metabolic Syndrome in Youths and Young Men Depending on the Degree of Purification and Reason of Obesity

“…Исследования показывают, что у подростков и юношей с ожирением данная патология сохраняется и во взрослом периоде жизни [4]. Известно, что гипоталамус управляет сложными физиологическими реакциями, такими как контроль пищевого поведения; энергетический обмен; циркадный ритм продукции гормонов; реактивность на стрессовые ситуации; фертильность [5]. С одной стороны, ожирение может способствовать нарушению регуляторной функции гипоталамуса [6].…”