Hormonal
Leptin resistance in obesity is likely caused by defective transport of leptin across the blood-brain barrier (BBB) and/or downregulation of hypothalamic leptin receptors, rather than a lack of leptin production.
Standard leptin injections do not work for most obese people because the hormone cannot cross the blood-brain barrier efficiently or the brain receptors are downregulated. This is why 'leptin diets' or supplements are ineffective for common obesity. Effective interventions must either bypass the blood-brain barrier or target downstream pathways.
It has been postulated that leptin resistance might be due to defective leptin transport across the BBB... This suggests that leptin enters the brain by a saturable transport system and that the capacity of leptin transport is lower in obese individuals... One other possibility is that a defect in leptin receptor expression in the hypothalamus is the cause of altered leptin sensitivity.
Why this rating
Supported by multiple studies cited in the review regarding BBB transport and receptor mRNA levels.
Source
The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review
Melanie D. Klok et al. · Obesity Reviews · 2006
DOI 10.1111/j.1467-789x.2006.00270.x
More from this paper
- In obese humans, circulating leptin levels are elevated while ghrelin levels are decreased, and the body exhibits leptin resistance, meaning high leptin fails to suppress food intake or increase energy expenditure as it does in lean individuals.Good
- Ghrelin functions as a meal-initiation signal in humans, with preprandial increases correlating with hunger, and its levels are suppressed by food intake, although its role in long-term weight regulation is less clear than leptin's.Good
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