Читать книгу Clinical Obesity in Adults and Children - Группа авторов - Страница 80

In 1997, we reported two severely obese cousins from a highly consanguineous family of Pakistani origin [28]. Both children had undetectable levels of serum leptin and were found to be homozygous for a frameshift mutation in the ob gene, which resulted in a truncated protein that was not secreted. We and others have since identified other families with mutations in the leptin gene including some that result in proteins that are bioinactive [29]. All subjects in these families are characterized by severe early‐onset obesity and intense hyperphagia [30–32] with food‐seeking behavior and an inability to discriminate between appetizing and bland foods [33]. Although normal pubertal development did not occur, there was some evidence of a delayed but spontaneous pubertal development in one person [32].

We demonstrated that children with leptin deficiency had profound abnormalities of T cell number and function [30], consistent with high rates of childhood infection and a high reported rate of childhood mortality from infection in obese Turkish subjects. Most of these phenotypes closely parallel those seen in murine leptin deficiency. However, there are some phenotypes where the parallels between humans and mice are not as clear‐cut. The contribution of reduced energy expenditure to the obesity of the ob/ob mouse is well established [34]. In leptin‐deficient humans, we found no detectable changes in resting or free‐living energy expenditure [30]. Ozata et al. reported abnormalities of sympathetic nerve function in leptin‐deficient humans consistent with defects in the efferent sympathetic limb of thermogenesis [32].