The heat-shock response, one of the main pro-survival mechanisms of a living organism, has evolved as the biochemical response of cells to cope with heat stress. The most well-characterized aspect of the heat-shock response is the accumulation of a conserved set of proteins termed heat-shock proteins (HSPs). HSPs are key players in protein homeostasis acting as chaperones by aiding the folding and assembly of nascent proteins and protecting against protein aggregation. HSPs have been associated with neurological diseases in the context of their chaperone activity, as they were found to suppress the aggregation of misfolded toxic proteins. In recent times, HSPs have proven to have functions apart from the classical molecular chaperoning in that they play a role in a wider scale of neurological disorders by modulating neuronal survival, inflammation, and disease-specific signaling processes. HSPs are gaining importance based on their ability to fine-tune inflammation and act as immune modulators in various bodily fluids. However, their effect on neuroinflammation processes is not yet fully understood. In this review, we summarize the role of neuroinflammation in acute and chronic pathological conditions affecting the brain. Moreover, we seek to explore the existing literature on HSP-mediated inflammatory function within the central nervous system and compare the function of these proteins when they are localized intracellularly compared to being present in the extracellular milieu.

Inappropriate nutrition and a sedentary lifestyle can lead to obesity, one of the most common risk factors for several chronic diseases. Although regular physical exercise is an efficient approach to improve cardiometabolic health, the exact cellular processes are still not fully understood. We aimed to analyze the morphological, gene expression, and lipidomic patterns in the liver and adipose tissues in response to regular exercise. Healthy (wild type on a normal diet) and hyperlipidemic, high-fat diet-fed (HFD-fed) apolipoprotein B-100 (APOB-100)-overexpressing mice were trained by treadmill running for 7 months. The serum concentrations of triglyceride and tumor necrosis factor α (TNFα), as well as the level of lipid accumulation in the liver, were significantly higher in HFD-fed APOB-100 males compared to females. However, regular exercise almost completely abolished lipid accumulation in the liver of hyperlipidemic animals. The expression level of the thermogenesis marker, uncoupling protein-1 (Ucp1), was significantly higher in the subcutaneous white adipose tissue of healthy females, as well as in the brown adipose tissue of HFD-fed APOB-100 females, compared to males. Lipidomic analyses revealed that hyperlipidemia essentially remodeled the lipidome of brown adipose tissue, affecting both the membrane and storage lipid fractions, which was partially restored by exercise in both sexes. Our results revealed more severe metabolic disturbances in HFD-fed APOB-100 males compared to females. However, exercise efficiently reduced the body weight, serum triglyceride levels, expression of pro-inflammatory factors, and hepatic lipid accumulation in our model.