Leptin Resistance and Cardiometabolic Disorders: Bridging Molecular Pathways, Genetic Variants, and Therapeutic Innovation.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic and clinical concepts without primary data or systematic search
PubMed 39931847 · doi:10.2174/011573403X356019250118170444
What was done
This narrative review synthesized the molecular mechanisms of leptin signaling (primarily the hypothalamic JAK2/STAT3 pathway), the pathophysiology of leptin resistance in central and peripheral tissues (pancreas, liver, muscle), genetic variants in the LEPR gene, and potential therapeutic strategies such as leptin replacement, chemical chaperones, and SOCS3/PTP1B inhibitors.
What was found
The abstract reports no numerical findings or effect sizes. It qualitatively describes that obesity leads to hyperleptinemia and reduced leptin responsiveness, exacerbating chronic inflammation, oxidative stress, endothelial dysfunction, and insulin resistance. It also notes that LEPR gene variants correlate with elevated stroke risk and that emerging targeted therapies may restore leptin sensitivity and improve metabolic profiles.
Why it matters
The review provides a comprehensive mechanistic overview connecting leptin signaling pathways to cardiovascular and metabolic diseases, identifying specific molecular targets for overcoming leptin resistance.
Limits
The paper is a narrative review presenting no primary clinical or experimental data, systematic search criteria, or quantitative pooled estimates. Specific sample sizes and effect magnitudes are absent from the abstract.
Cited by
- context Leptin is released into the blood following a meal and acts on the hypothalamus to signal satiety.