Obesity-Related Neuroinflammation: Magnetic Resonance and Microscopy Imaging of the Brain

Abstract

Obesity is a major risk factor of Alzheimer’s disease and related dementias. The principal feature of dementia is a loss of neurons and brain atrophy. The mechanistic links between obesity and the neurodegenerative processes of dementias are not fully understood, but recent research suggests that obesity-related systemic inflammation and subsequent neuroinflammation may be involved. Adipose tissues release multiple proinflammatory molecules (fatty acids and cytokines) that impact blood and vessel cells, inducing low-grade systemic inflammation that can transition to tissues, including the brain. Inflammation in the brain—neuroinflammation—is one of key elements of the pathobiology of neurodegenerative disorders; it is characterized by the activation of microglia, the resident immune cells in the brain, and by the structural and functional changes of other cells forming the brain parenchyma, including neurons. Such cellular changes have been shown in animal models with direct methods, such as confocal microscopy. In humans, cellular changes are less tangible, as only indirect methods such as magnetic resonance (MR) imaging are usually used. In these studies, obesity and low-grade systemic inflammation have been associated with lower volumes of the cerebral gray matter, cortex, and hippocampus, as well as altered tissue MR properties (suggesting microstructural variations in cellular and molecular composition). How these structural variations in the human brain observed using MR imaging relate to the cellular variations in the animal brain seen with microscopy is not well understood. This review describes the current understanding of neuroinflammation in the context of obesity-induced systemic inflammation, and it highlights need for the bridge between animal microscopy and human MR imaging studies.

Body size interacts with the structure of the central nervous system: A multi-center in vivo neuroimaging study

“…96 Although precise pathophysiological processes are not well known today, it is certain that obesity causes neuroinflammation, thus, alters brain microstructure and increases risks of neurodegenerative disorders such as Alzheimer's disease and other types dementias. 97 Our DTI and MTR data acquired in the current healthy population with low-to-moderate BMI may point to a borderline trend between homeostasis and mild microstructural changes related to the higher body weight. The negative correlation between body weight and MTR has also recently been reported in peripheral nerves and skeletal muscles.…”

Childhood Obesity, Hypothalamic Inflammation, and the Onset of Puberty: A Narrative Review

“…These changes involve how the brain responds to external stimuli like food-related signals, taste, and scent, as well as alterations in its baseline activity, patterns of activation, and connectivity during different cognitive activities such as learning, impulsive decision making, inhibitory control, memory, and attention [ 42 ]. Brain imaging in animal studies reveals that diet-induced obesity results in morphological alterations of various cell types, including oligodendrocytes, microglia, astrocytes, and neurons [ 43 ]. Obese subjects, as shown by MRI scans, display elevated hypothalamic gliosis, which is corroborated by histological evidence revealing amplified microglia activation in individuals with a BMI exceeding 30 compared to those with a BMI below 25 [ 44 ].…”

“…Microglia also accumulate lipid droplets under inflammatory conditions, compromising their phagocytic function [ 57 ]. These observed cellular changes in the brain in obesity and inflammation need further investigation to understand their relationship with the observed volumetric and tissue magnetic resonance properties [ 43 ].…”

Harm! foul! How acute kidney injury SHReDDs patient futures

“…The suggestion that AKI induces intracranial inflammation and vascular changes implicated in stroke pathogenesis may prove a starting point toward further clinical investigation and screening. Significant advances in assessment of intracranial inflammation such as novel-contrast MRI, molecular imaging, and cerebrospinal fluid biomarkers may provide avenues for translational study [12,13].…”