Chronic inflammation in obesity and neurodegenerative diseases: exploring the link in disease onset and progression

Obesity, a worldwide health emergency, is defined by excessive fat accumulation and significantly impacts metabolic health. In addition to its recognized association with cardiovascular disease, diabetes, and other metabolic illnesses, recent studies have revealed the connection between obesity and neurodegeneration. The main reason for this link is inflammation caused by the growth of fat tissue, which activates harmful processes that affect how the brain works. Fat tissue, particularly the fat around the organs, produces various substances that cause inflammation, such as cytokines (TNF-α, IL-6), adipokines (leptin, resistin), and free fatty acids. These chemicals cause low-grade, persistent systemic inflammation, which is becoming more widely acknowledged as a major factor in peripheral metabolic dysfunction and pathology of the central nervous system (CNS). Inflammatory signals in the brain cause neuroinflammatory reactions that harm neuronal structures, change neuroplasticity, and disrupt synaptic function. When obesity-related inflammation is present, the brain's resident immune cells, known as microglia, become hyperactivated, which can lead to the production of neurotoxic chemicals, which can cause neuronal death. This neuroinflammation exacerbates the negative effects of obesity on brain health and is linked to cognitive decline, Alzheimer's disease, and other neurodegenerative disorders. Moreover, the blood-brain barrier (BBB) exhibits increased permeability during inflammatory states, facilitating the infiltration of peripheral immune cells and cytokines into the brain, hence exacerbating neurodegeneration. Adipose tissue is a source of chronic inflammatory mediators, which are examined in this review along with the molecular pathways that connect inflammation brought on by obesity to neurodegeneration. Additionally, it addresses various anti-inflammatory treatment approaches, including lifestyle modifications, anti-inflammatory medications, and gut microbiota modulation, to lessen the metabolic and neurological effects of obesity. Recognizing the link between obesity and inflammation opens up new opportunities for early intervention and the development of targeted treatments to prevent or alleviate neurodegenerative disorders.