Sinan Caglayan

Leptin Replacement Prevents Weight Loss-Induced Metabolic Adaptation in Congenital Leptin-Deficient Patients

CONTEXT Leptin regulates energy homeostasis by suppressing food intake; however, its role in energy expenditure and fat oxidation remains uncertain in humans. OBJECTIVE The aim of the study was to assess 24-h energy metabolism before and after weight loss induced by leptin treatment in congenital leptin-deficient subjects or low-calorie diet in controls. DESIGN AND PATIENTS We measured 24-h energy expenditure, 24-h fat oxidation, and body fat in three null homozygous leptin-deficient obese adults before and after weight loss induced by a 19-wk leptin replacement period (0.02-0.04 mg/kg/d). The same measures were performed in three obese controls pair-matched for sex, age, and weight loss induced by a 10- to 21-wk low-calorie diet. Measurements were preceded for 1 wk of weight stabilization. Energy expenditure was adjusted for fat-free mass, fat mass, sex, and age based on a reference population (n = 842; R(2) = 0.85; P < 0.0001). Similarly, fat oxidation was adjusted for fat-free mass, percentage body fat, energy balance, and diet composition during the 24-h respiratory chamber stay (R(2) = 0.38; P < 0.0001). RESULTS Before weight loss, congenital leptin-deficient and control subjects had similar energy expenditure. However, after weight loss ( approximately 15 kg), controls had energy expenditures lower than expected for their new weight and body composition (-265 +/- 76 kcal/d; P = 0.04), whereas leptin-treated subjects had values not different from the reference population (-128 +/- 119 kcal/d; P = 0.67). Before weight loss, fat oxidation was similar between groups. However, after weight loss, leptin-treated subjects had higher fat oxidation than controls (P = 0.005) and higher than the reference population (P = 0.0001). CONCLUSION In congenital leptin-deficient subjects, leptin replacement prevented the decrease in energy expenditure and fat oxidation often observed after weight loss.

Microanalysis of eating behavior of three leptin deficient adults treated with leptin therapy

Leptin deficiency has been associated with extreme obesity and hyperphagia in rodents and humans. A rare genetic disorder in humans yields the absence of the hormone leptin, extreme obesity, and a ravenous appetite. Reports on these rare cases have indicated that therapy using leptin injections can yield significant weight loss and changes in appetite. The aim of this report on acute leptin therapy in three leptin deficient adults was to provide a microanalysis of changes in eating behavior and ratings of hunger and satiety. In addition to substantial weight loss, 15 weeks of leptin therapy was associated with approximately 50% reduction in food intake and substantial changes in ratings of hunger and satiety before most meals. After short-term leptin therapy, the three participants ate until ratings indicated they were satiated, which was comparable to the ratings before leptin therapy. These findings suggest that one of the primary effects of acute leptin therapy may be to reduce the ravenous hunger associated with leptin deficiency, resulting in reduced food intake and significant weight loss. These results are discussed in the context of the scientific literature pertaining to leptin and its effects on appetite and obesity.

Mitochondrial DNA common deletion is not associated with thyroid, breast and colorectal tumors in Turkish patients

Recently, efforts have been focused on mitochondrial DNA changes and their relation to human cancers. Among them, a 4977 bp deletion of mitochondrial DNA, named “common deletion”, has been investigated in several types of tumors, with inconsistent results. In this study, we investigated the presence of the common deletion in tissues from 25 breast, 25 colorectal and 50 thyroid tumors and in the adjacent healthy tissues from Turkish patients. Samples from healthy volunteers were also evaluated for comparison. Two PCR-based methods were used for the detection of the common deletion. First, two pairs of primers were used to amplify wild-type and deleted mtDNA. Then, a highly sensitive nested-PCR was performed, to determine low amounts of deleted genomes. By the first method, wild-type mtDNAs were observed in all samples, but a deletion was observed in only six thyroid samples, by using the nested-PCR method. In conclusion, the mitochondrial common deletion was very rare in our study group and did not appear to be not related with cancer.

Event-related brain potentials in male hypogonadism

Several studies based on psychometric tests have determined an impairment of cognitive functions in patients with androgen deficiency. However, little is known about event-related potentials (ERPs) alterations in male hypogonadism. We investigated alterations of ERP in male hypogonadism before and 3 months after gonadotropin treatment. ERPs were elicited in 20 untreated male patients with idiopathic hypogonadotropic hypogonadism (IHH) (mean age: 21.1±1.4 years) and in a group of 30 male controls with comparable mean age and educational level. ERP recordings were repeated 3 months after hCG/hMG treatment. Untreated hypogonadal patients had longer mean P300 latencies and increased P300 amplitudes when compared to those in controls (321.6±18.5 vs 299.3±20.1 msec, p=0.0002; 12.15±4.47 vs 9.38±3.02μV, p=0.011, respectively). The mean P300 latencies did not change significantly 3 months after gonadotropin treatment, while P300 amplitudes were decreased significantly. P300 latencies did not correlate with serum testosterone and other hormone levels. We conclude that prolongation of P300 latencies and increased P300 amplitudes are associated with male hypogonadism, but P300 prolongation is not reversed 3 months after gonadotropin treatment. These findings confirm the occurrence of cognitive defects in hypogonadal patients and would support the hypothesis that perinatal androgen deficiency contributes to an insufficient cognitive development.

An experimental therapeutic approach to genetically-based obesity

Genetic mutations in the leptin pathway can be a cause of human obesity. We examined the effects of human leptin replacement in the only three adults identified to date who have genetically‐based leptin deficiency. Their phenotype consisted of morbid obesity, with hypogonadism, but without hypertension or hyperlipidemia.