Does Childhood Obesity Trigger Neuroinflammation?

Abstract

Childhood obesity is constantly increasing around the world, and it has become a major public health issue. Considerable evidence indicates that overweight and obesity are important risk factors for the development of comorbidities such as cognitive decline, neuroinflammation and neurodegenerative diseases. It is known that during obesity, adipose tissue undergoes immune, metabolic and functional changes which could induce a neuroinflammatory response of the central nervous system (CNS). In this context, to inspect if obesity can start to trigger the neuroinflammation from a pediatric age, we surgically collected and analyzed adipose tissue from the periumbilical area of three obese children (AT-OB) and two normal-weight children (AT-Ctrl). We considered the transcriptomic profile of our samples to detect alterations in different biological processes that might be also involved in the inflammatory and neuroinflammatory response. Our results show alterations of lipid and fatty acids metabolism in AT-OB compared to the AT-Ctrl. We also observed an onset of inflammatory response in AT-OB. Interestingly, among the genes involved in neuroinflammation, GRN and SMO were upregulated, while IFNGR1 and SNCA were downregulated. Our study highlights that obesity may trigger inflammation and neuroinflammation from a pediatric age.

NHANES 2011–2014 Reveals Decreased Cognitive Performance in U.S. Older Adults with Metabolic Syndrome Combinations

“…It was previously considered that childhood obesity was not overtly associated with lipidic or glycemic disturbances, but rather “simply” associated with increasing and steady weight gain. However, recent transcriptomic data from adipose tissue from obese children show severe alteration in the lipid and fatty acid metabolism pathway [ 78 ], suggesting that weight gain and obesity is the earliest component to develop and would probably drive overall systemic inflammation progression, even from pediatric ages.…”

“…These different results can be due to the neuronal regions that are more susceptible to inflammation-induced damage. Obesity-induced inflammation induces changes in blood–brain barrier permeability that favor leukocyte migration and inflammatory signals [ 78 ]. Neurons need a degree of “sturdiness” to survive age progression and accumulation of damaged proteins, as they are not able to return into S-phase and replicate.…”

Subcutaneous Adipose Tissue Transcriptome Highlights Specific Expression Profiles in Severe Pediatric Obesity: A Pilot Study

“…To date, microarray analyses of blood cells, isolated adipocytes, adipose tissue, or stromal vascular fractions make up nearly all published studies, and, in some cases, children are grouped together without considering the differences between normal weight and obesity [ 27 ]. However, a few RNA-seq studies have been performed on the AT of children or adolescents [ 28 , 29 ]. In their work, Sheldon and colleagues compared intra-abdominal AT collected from severely obese adolescents in relation to different stages of NAFLD [ 28 ].…”

“…In their work, Sheldon and colleagues compared intra-abdominal AT collected from severely obese adolescents in relation to different stages of NAFLD [ 28 ]. In addition, a pilot study by Zingale et al focused on the expression of neuro-inflammatory markers, proposing a relationship between obesity and neuro-inflammation [ 29 ].…”

“…The pathway analysis of the coding DEGs revealed their associations with several signaling cascades, including the metabolic, hippo signaling, oxytocin, apelin, and HIF-1α pathways, proving that our data are consistent with previous observations reported in the literature [ 34 , 35 , 36 , 37 ]. A recent RNA-seq report on periumbilical scAT from children with obesity and normal weight revealed a significant deregulation in several coding DEGs implied in fatty acid and carbohydrate metabolisms, as well as in inflammatory pathways [ 29 ]. In our study, we did not observe any differences between the OB and NW groups.…”