Adipose–Liver–Brain Redox Crosstalk in Obesity-Associated Cognitive Vulnerability: A Narrative Review

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Abstract
Background: Obesity-associated cognitive vulnerability involves peripheral metabolic organs, the circulation, and the neurovascular unit/blood–brain barrier (NVU/BBB). Whether adipose and hepatic dysfunction contribute through compartment-specific redox remodelling remains unclear. Methods: We searched PubMed/MEDLINE, Web of Science Core Collection, and Scopus for human, rodent, and cellular studies published from 1 January 2017 to 13 September 2026. Ninety-seven publications met the inclusion criteria. No meta-analysis or formal risk-of-bias assessment was undertaken. Results: Human studies associated adipose or hepatic dysfunction and circulating redox markers with brain and cognitive outcomes but rarely established tissue origin, temporal ordering, or mediation. Animal and cellular studies supported adipose mitochondrial and NOX-derived ROS, MASLD/MASH-related hepatic redox dysfunction, liver-derived signals, NVU/BBB impairment, and brain mitochondrial, inflammatory, synaptic, and cognitive changes. Conclusions: The adipose–liver–brain network is biologically plausible but remains unproven as a causal model. Future longitudinal and intervention studies should establish compartment specificity, temporal ordering, mediator reproducibility, reversibility, and domain-specific cognitive effects.
Funding Information
  • Hunan Provincial Education Commission Foundation (24A0683)
  • Hunan Provincial Education Commission Foundation (24B0885)
  • Hunan Provincial Education Commission Foundation (25A0803)
  • Hunan Provincial Education Commission Foundation (24C0604)
  • National College Students’ Innovative Entrepreneurial Training Plan Program (S202410823019)
  • National College Students’ Innovative Entrepreneurial Training Plan Program (S202410823020)
  • National College Students’ Innovative Entrepreneurial Training Plan Program (S202510823041)
  • Innovation and Entrepreneurship Education Base of Public Health and Preventive Medicine (333-93)
  • “The 14th Five-Year Plan” Application Characteristic Discipline of Hunan Province
  • Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province, China

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