The Influence of Adipose Tissue on Brain Development, Cognition, and Risk of Neurodegenerative Disorders

Abstract

The brain is a highly metabolic organ and thus especially vulnerable to changes in peripheral metabolism, including those induced by obesity-associated adipose tissue dysfunction. In this context, it is likely that the development and maturation of neurocognitive circuits may also be affected and modulated by metabolic environmental factors, beginning in utero. It is currently recognized that maternal obesity, either pre-gestational or gestational, negatively influences fetal brain development and elevates the risk of cognitive impairment and neuropsychiatric disorders in the offspring. During infancy and adolescence, obesity remains a limiting factor for healthy neurodevelopment, especially affecting executive functions but also attention, visuospatial ability, and motor skills. In middle age, obesity seems to induce an accelerated brain aging and thus may increase the risk of age-related neurodegenerative diseases such as Alzheimer's disease. In this chapter we review and discuss experimental and clinical evidence focusing on the influence of adipose tissue dysfunction on neurodevelopment and cognition across lifespan, as well as some possible mechanistic links, namely the role of the most well studied adipokines.

Cold-induced lipid dynamics and transcriptional programs in white adipose tissue

“…A previous study indicated that thermogenesis stimulation improved metabolic deficits and protected a mouse model of AD [104]. Increasing evidence has suggested that adipose tissue influences brain development, cognition, and the risk for neurodegenerative disorders throughout one’s lifespan [105]. In this context, it is likely that the peripheral-derived metabolic changes in iWAT triggered by cold exposure may also provide beneficial effects on T2D and neurodegenerative disorders.…”

“…Functional enrichment analyses of genes with pronounced cold-induced expression in the present study revealed a set of genes associated with neurodegenerative disorders. Several adipokines have been implicated in AD, such as FGF21, adiponectin, and resistin [105]. The gene that encodes FGF21 was significantly increased, while the others tended to decrease in response to cold exposure in iWAT.…”

Integration of heterogeneous functional genomics data in gerontology research to find genes and pathway underlying aging across species

“…Ingenuity Pathway Analysis (IPA) showed the most highly significant pathways included “Behavior, Connective Tissue Development and Function, Tissue Morphology” which contained 12 of the 15 genes (likelihood 1 x 10 31 , Fisher’s exact test; Fig 2; and S3 Table). Emerging research supports the role of adipokines in adipose tissue dysfunction where they exert effects upon neurodevelopment and cognition across life span [27]. Identification of this pathway identifies potential translational targets for therapies for treating or preventing dementia in the aging obese population.…”

The Other Side of Alzheimer’s Disease: Influence of Metabolic Disorder Features for Novel Diagnostic Biomarkers

“…The metabolic alterations occurring in AD described in the previous paragraphs all contribute to the worsening of the neuroinflammation state that characterizes this disease [256,257]. In AD, impaired glucose metabolism and insulin resistance are deeply correlated to the chronic inflammation state [79] as well as to adipose tissue that releases numerous pro-inflammatory adipokines [104][105][106]110]. Moreover, mitochondria dysfunctions promote oxidative stress and energy metabolism impairment [144,146], while lysosomal alterations lead to an impairment of the autophagic pathway and of its general degradation activity [197,200,212].…”

“…The adipose tissue plays a central role in regulating the body energy and the homeostasis of glucose, both at organs and systemic levels [104][105][106][107][108]. In particular, adipose white tissue stores energy in the form of lipids and controls the mobilization and distribution of lipids in the body, while adipose brown tissue maintains body temperature and acts as an endocrine organ, producing numerous bioactive factors such as adipokines (e.g., Leptin, Adiponectin, Apelin, Resistin, Monocyte Chemoattractant Protein-1 (MCP-1), IL-1β, IL-6, IL-10, TNFα, Transforming Growth Factor β (TGF-β)) and lipokines (such as Lysophosphatidic Acid, LPA), which control many metabolic pathways including in the brain [104][105][106]109,110]. In particular, Leptin has pro-inflammatory activities, maintains neurogenesis and synaptogenesis, and is involved both in neuroprotection and neuroinflammation.…”