Human Leptin Deficiency Caused by a Missense Mutation: Multiple Endocrine Defects, Decreased Sympathetic Tone, and Immune System Dysfunction Indicate New Targets for Leptin Action, Greater Central than Peripheral Resistance to the Effects of Leptin, and Spontaneous Correction of Leptin-Mediated Defects

• DOI: 10.1210/jc.84.10.3686
• Publication Date: 2004-02-25T21:56:42Z
• Authors: M. Ozata
• Keywords: Sympathetic nervous system

We have previously demonstrated that genetically based leptin deficiency due to a missense gene mutation in highly consanguineous extended Turkish pedigree is associated with morbid obesity and hypogonadism. now performed detailed assessments of endocrine, sympathetic, immune function. also identified new adult female homozygous patient this family who severely obese amenorrheic. In all wild-type heterozygous individuals normal body weight. Seven members family, whom we presume been deficient, died during childhood. There are several findings indicate potentially novel targets for action humans. Four patients (1 male, 2 females, 1 child) sympathetic system dysfunction, whereas subjects Despite dysfunction postural hypotension, 3 has impaired renin-aldosterone The exhibit alterations GH PTH-calcium function, them decreased bone mineral density. their obesity, these do not risk factors cardiovascular disease, such as hypertension, impairments lipid metabolism, or hyperglycemia. These data support the hypothesis may central, but peripheral, resistance effects hyperglycemia mediate morbidity deficient. Furthermore, there be human physiology. Such lead pharmacological strategies use agonists antagonists treatment disease. All 19 weight alive, 7 11 childhood after infections. odds ratio mortality context phenotype 25.4, indicating impairs key biological functions childhood, negatively impacting on survival. found only child had thyroid function abnormalities. oldest started menstruate, albeit luteal phase defect, months ago, delay over 20 yr, younger still hypogonadic. Thus, conclude long life span, humans survive negative can, contrast ob/ob mice, decades compensate some immunity endocrine through mechanisms remain elucidated.