Hormonal
Leptin resistance in obesity is primarily driven by impaired transport of leptin across the blood-brain barrier and intracellular signaling defects (specifically JAK2-STAT3 pathway inhibition by SOCS3 and PTP1B), rather than leptin deficiency.
If you are obese, your body likely produces plenty of leptin, but your brain is ignoring it. This is not because you lack the hormone, but because of biological 'noise' (inflammation, transport issues) blocking the signal. Simply taking leptin supplements is ineffective because the resistance mechanism prevents the hormone from acting on the brain. Focus on reducing the factors that cause this resistance, such as inflammation and high blood-brain barrier permeability issues, rather than seeking leptin replacement.
A minor increase in leptin concentration reduces the appetite and leads to a decrease in body weight; however, in obesity, despite increased leptin concentration, the efficacy of the anorexic effect of leptin is decreased, with leptin resistance developing due to a defect in intracellular signaling associated with the leptin receptor or decreases in leptin transport across the blood–brain barrier (BBB).
Why this rating
The paper is a comprehensive review citing multiple human and animal studies, though it notes a lack of clear diagnostic criteria.
Source
<p>Leptin resistance: underlying mechanisms and diagnosis</p>
О. В. Груздева et al. · Diabetes Metabolic Syndrome and Obesity · 2019
DOI 10.2147/dmso.s182406
More from this paper
- High serum leptin levels (>25-30 ng/mL) saturate the blood-brain barrier transport system, preventing leptin from entering the brain and thereby contributing to leptin resistance.Good
- Hypothalamic inflammation and endoplasmic reticulum stress are key drivers of leptin resistance, mediated by inflammatory cytokines like IL-6 and TNF-alpha induced by high-fat diets.Good
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