Hormonal
Leptin resistance, a primary risk factor for obesity, results from impaired leptin transport across the blood-brain barrier, defective LEPRb signaling (via SOCS3 and PTP1B), and disrupted hypothalamic neurocircuitry.
Obesity is not just about calories; it involves a broken hormonal signal (leptin) that fails to tell your brain to stop eating and burn fat. This failure happens due to transport issues, receptor signaling blocks (like SOCS3), and neural circuit changes. Treating obesity requires addressing these biological resistance mechanisms, not just willpower.
Leptin resistance, a primary risk factor for obesity, likely results from impairment in leptin transport, LEPRb signaling, and/or the neurocircuitry of energy balance.
Why this rating
This is a high-impact review article in a top physiology journal citing 226 articles, establishing the consensus mechanism.
Source
Recent advances in understanding leptin signaling and leptin resistance
David L. Morris et al. · American Journal of Physiology-Endocrinology and Metabolism · 2009
DOI 10.1152/ajpendo.00274.2009
More from this paper
- Leptin regulates energy balance primarily by acting on the hypothalamus (specifically ARC, VMH, PVH) to activate LEPRb, which triggers downstream pathways (STAT3, PI3K, MAPK) to suppress appetite and increase energy expenditure.Strong
- Peripheral leptin action (on pancreas, muscle, liver) is not required for normal energy balance or body weight regulation in mice, as peripheral LEPRb deletion does not alter these metrics.Good
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