Targeting the Adipose-Brain Axis: Adipokines as Key Modulators of Cognitive Dysfunction

Area of Science:

• Neuroscience
• Endocrinology
• Metabolic Syndrome

Background:

• Adipose tissue functions as an endocrine organ, secreting adipokines that influence brain function via metabolic, inflammatory, vascular, and neurotrophic pathways.
• Dysregulated adipokine signaling is implicated in cognitive decline and neurodegeneration, affecting neuronal energy metabolism, mitochondrial function, insulin signaling, and synaptic plasticity.
• Adipokines contribute to oxidative stress and neuroinflammation, further impacting brain health.

Purpose of the Study:

• To review and discuss the roles of adipokines in maintaining brain health, with a specific focus on cognitive function.
• To synthesize findings from preclinical and clinical studies on the adipose-brain axis and its relation to cognition.

Main Methods:

• Systematic literature search using keywords and MeSH terms related to adipokines, brain, cognition, and neurodegenerative diseases.
• Inclusion of studies examining adipokine signaling pathways, their impact on neuronal function, and clinical associations with cognitive outcomes.

Main Results:

• Preclinical data show neuroprotective effects of leptin, adiponectin, and CTRP3 via AMPK, PI3K/Akt, and sirtuin pathways.
• Conversely, resistin, DPP-4, ANGPTL4, and visfatin may promote neurodegeneration by inducing insulin resistance, amyloidogenesis, mitochondrial dysfunction, and inflammation.
• Clinical studies in aging populations reveal complex associations, with elevated adipokines sometimes linked to poorer cognitive outcomes, possibly due to resistance or metabolic dysregulation.

Conclusions:

• Adipokines represent potential biomarkers for cognitive decline and therapeutic targets for the adipose-brain axis.
• Modulating adipokine signaling may offer strategies to prevent or mitigate cognitive impairment and neurodegeneration.