Severe obesity with hypo-leptinemia

Some cases of obesity are thought to be associated with hypo-leptinemia. This may cause decreased appetite suppression resulting in increased appetite, leading to weight gain. Replacement therapy with leptin might be theoretically useful, but verification by reporting more cases is required. Here, we first investigated the serum leptin levels and their correlation with body mass index (BMI) in 107 patients with obesity to identify the subjects with hypo-leptinemia. Among them, one patient with congenital hypopituitarism was further investigated by comparison of his clinical and pathological characteristics with those of control subjects. This 40-year-old Japanese man, who was large from birth, consistently showed obesity of more than 2SD during his growth period. He had 41.5 kg/m² at BMI with central hypogonadism, central diabetes insipidus and severe growth hormone deficiency, cognitive impairment, and abnormal eating behavior, which led to suspicion of the involvement of hypothalamic factors. Genetic analysis revealed no definite mutations regarding metabolic and nutritional systems or adipocytes including leptin-related genes. Electron microscopic images of subcutaneous adipose tissue demonstrated relatively smaller adipocytes compared with a BMI-matched patient. The patient suffered from his abnormal eating behavior, began dialysis at the age of 41 years, and died of bacterial pneumonia at 49 years of age. Among patients with severe obesity with hypo-leptinemia, there could be patients with disturbance of healthy expansion in adipocyte, probably due to unknown dysfunction. Even with the lack of abnormality of leptin-related genes, indication of leptin-replacement may be considered for severely obese patients with hypo-leptinemia.