Leptin Receptor Compound Heterozygosity in Humans and Animal Models

Leptin and its receptor are essential for regulating food intake, energy expenditure, glucose homeostasis and fertility. Mutations within leptin or the leptin receptor cause early-onset obesity and hyperphagia, as described in human and animal models. The effect of both heterozygous and homozygous variants is much more investigated than compound heterozygous ones. Recently, we discovered a spontaneous compound heterozygous mutation within the leptin receptor, resulting in a considerably more obese phenotype than described for the homozygous leptin receptor deficient mice. Accordingly, we focus on compound heterozygous mutations of the leptin receptor and their effects on health, as well as possible therapy options in human and animal models in this review.

Automated summary

Leptin and its receptor play crucial roles in regulating food intake, energy expenditure, glucose homeostasis, and fertility. Mutations within leptin or the leptin receptor can result in early-onset obesity and hyperphagia. Recent research has shown that compound heterozygous mutations within the leptin receptor may lead to a considerably more obese phenotype compared to homozygous mutations, sparking interest in exploring the effects of compound heterozygous mutations on health in both human and animal models.