Os impactos da obesidade na maquinaria mitocondrial hipotalâmica: uma revisão narrativa

Abstract

Obesity has reached pandemic levels, affecting more than a billion people globally, and a considerable increase is projected in the coming years. This chronic disease is a notable disruptor for several metabolic and neurodegenerative comorbidities, imposing a substantial burden on healthcare systems. Physiologically, adipose tissue (TA) hypertrophied, acting as an endocrine organ, secretes inflammatory adipokines (TNF-α and IL-6), establishing meta-inflammation. Nutrient overload and excess acids Free fatty acids (FFAs) lead to systemic mitochondrial dysfunction. This dysfunction deregulates the mitochondrial dynamics, resulting in excessive production of Reactive Oxygen Species (ROS) and subsequent oxidative stress (OS). The hypothalamus, crucially dependent on energy for the regulation of metabolism, is impacted by diet-induced obesity (OID). OID causes hypothalamic mitochondrial dysfunction, characterized by OS and changes in dynamics, such as the attenuation of fusion proteins (Mfn1 and Mfn2) and the increase fission protein (DRP1). This mitochondrial fragmentation, especially in neurons POMC (anorectics), mitigates its activity and is an important component of resistance to leptin and insulin. In short, the elucidation of this intrinsic relationship between obesity, OS, chronic inflammation and dysregulation of hypothalamic mitochondrial machinery is fundamental for development