An important contributor to leptin resistance is changes to leptin receptor signalling, particularly in the arcuate nucleus , however, deficiency of, or major changes to, the leptin receptor itself are not thought to be a major cause. Insights from mouse models of obesity". In , a non-obese mouse colony being studied at the Jackson Laboratory produced a strain of obese offspring, suggesting that a mutation had occurred in a hormone regulating hunger and energy expenditure. Crit Rev Food Sci Nutr. The insulin increase in response to the caloric load provokes a dose-dependent rise in leptin, an effect potentiated by high cortisol levels. Treatment with metreleptin led to "rapid change in eating behavior, a reduction in daily energy intake, and substantial weight loss". A single case of a homozygous transversion mutation of the gene encoding for leptin was reported in January
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