Obesity and Cognitive Function: Leptin Role Through Blood-Brain Barrier and Hippocampus

Area of Science:

• Neuroscience
• Metabolic Disorders
• Endocrinology

Background:

• Adipokines from adipose tissue regulate CNS functions, influencing metabolic and neurological health.
• Obesity-induced changes, particularly dysregulated leptin, are linked to cognitive impairment and neurodegenerative diseases like Alzheimer's.
• Mechanisms linking peripheral obesity to central nervous system dysfunction and blood-brain barrier integrity are under investigation.

Purpose of the Study:

• To review and synthesize current literature on the role of leptin in obesity-associated cognitive decline and Alzheimer's disease pathogenesis.
• To elucidate the molecular mechanisms by which obesity affects blood-brain barrier function and central nervous system integrity via leptin signaling.
• To identify potential therapeutic targets for managing cognitive impairment in obesity.

Main Methods:

• An extensive electronic literature search was conducted across Web of Science, Scopus, and PubMed.
• English-language articles published between 2010 and 2025 were included.
• The review focused on studies investigating leptin's role in obesity and neurodegenerative diseases.

Main Results:

• Obesity dysregulates leptin secretion, leading to metabolic abnormalities and hippocampal synaptic disturbances.
• Obesity elevates inflammatory molecules that impair amyloid-beta clearance and promote its brain accumulation.
• Leptin signaling modulation in obesity contributes to cognitive decline and blood-brain barrier dysfunction.

Conclusions:

• Leptin signaling plays a critical role in the interplay between obesity, cognitive function, and Alzheimer's disease.
• Targeted strategies, including leptin sensitization and blood-brain barrier protective interventions, show promise for therapeutic development.
• Understanding leptin-driven mechanisms is crucial for developing effective treatments for obesity-related cognitive impairment.