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

Area of Science:

• Neuroscience
• Endocrinology
• Metabolic research

Background:

• Adipose tissue secretes adipokines that influence brain function via metabolic, inflammatory, vascular, and neurotrophic pathways.
• Dysregulated adipokine signaling is linked to cognitive decline and neurodegeneration by affecting neuronal metabolism, mitochondrial function, insulin signaling, and synaptic plasticity.
• Adipokines can amplify oxidative stress and neuroinflammation, contributing to brain dysfunction.

Purpose of the Study:

• To review and discuss the roles of adipokines in brain health, focusing on cognitive function.
• To synthesize findings from preclinical and clinical studies on the adipose-brain axis and cognition.

Main Methods:

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

Main Results:

• Preclinical data show neuroprotective effects of leptin, adiponectin, and CTRP3 via AMPK, PI3K/Akt, sirtuin, and anti-inflammatory pathways.
• Resistin, DPP-4, ANGPTL4, and visfatin may promote neurodegeneration by increasing insulin resistance, amyloid processing, mitochondrial dysfunction, oxidative stress, and inflammation.
• Clinical studies in aging populations show complex associations between elevated adipokines and poorer cognitive outcomes, possibly due to resistance or metabolic dysregulation.

Conclusions:

• Adipokines serve as potential biomarkers for cognitive decline.
• Modulating the adipose-brain axis through adipokines offers therapeutic targets for preventing or slowing cognitive decline.