Abstract
Obesity is a predisposing factor for numerous morbidities, including those affecting the central nervous system. Hypothalamic inflammation is a hallmark of obesity and is believed to participate in the onset and progression of the obese phenotype, by promoting changes in neuronal functions involved in the control of metabolism. The activation of brain immune cells in the hypothalamus, which are represented by microglia and brain macrophages, is associated with obesity and has been the focus of intense research. Despite the significant body of knowledge gathered on this topic, obesity-induced metabolic changes in brain cells involved in innate immune responses are still poorly characterized due, at least in part, to limitations in the existing experimental methods. Since the metabolic state influences immune responses of microglia and other myeloid cells, the understanding and characterization of the effects of cellular metabolism on the functions of these cells, and their impact on brain integrity, are crucial for the development of efficient therapeutic interventions for individuals exposed to a long-term high fat diet (HFD). Here we review and speculate on the cellular basis that may underlie the observed changes in the reactivity and metabolism of the innate immune cells of the brain in diet-induced obesity (DIO), and discuss important points that deserve further investigation.
Highlights
According to the World Health Organization, obesity has almost tripled since 1975 and is considered a worldwide epidemic, affecting more than 650 million people1
How do the findings reported in macrophages apply to microglia? While it is expected that signals triggered by PAMPs and DAMPs follow quite similar pathways in different myeloid cells, it is important to mention that resident brain cells present unique and remarkable features
It is unclear whether microglial metabolism is rewired, due to obesity-associated metabolic cues in vivo, or how this could occur
Summary
According to the World Health Organization, obesity has almost tripled since 1975 and is considered a worldwide epidemic, affecting more than 650 million people. Inflammation in brain areas, other than the hypothalamus, might certainly contribute to the onset and progression of some of the central pathologies associated with obesity, hypothalamic inflammation was previously shown to play a central role in disease processes, affecting the control of energy intake and energy expenditure (Velloso and Schwartz, 2011). These inflammation-induced alterations in the mediobasal hypothalamus (MBH) directly impact the integrity of homeostatic processes, such as hepatic glucose storage and delivery into the blood (Mravec et al, 2018). Pro-inflammatory signaling in the hypothalamus is a key event in the onset of DIO, the widespread inflammation and metabolic changes promoted by a HFD may further impact the hypothalamus
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