ABSTRACT
RESEARCH AIM: Nicotinamide phosphoribosyltransferase (Nampt) is an adipocytokine that is elevated in obesity, type 2 diabetes and increased levels are associated with inflammatory processes. Nampt serum concentrations have been suggested to follow a diurnal rhythm peaking in the afternoon in lean males. However, no data exists regarding the effects of gender and body weight. MATERIAL AND METHODS: We measured Nampt serum levels over 24 h in a cohort of healthy individuals living with either normal weight or obesity. Furthermore, effects of meals, oral glucose tolerance test and physical exercise on Nampt concentrations were evaluated. Correlation analyses to other hormonal- and lab parameters and anthropometric measurements were performed. RESULTS: Nampt showed a diurnal rhythm with increased levels at daytime and a peak in the early afternoon. This diurnal rhythm was significant for all groups but obese males. The Nampt amplitude, measured both relatively and absolutely, was significantly higher in females than in males. Meals did not influence Nampt serum levels, whereas physical exercise and an OGTT did significantly influence Nampt serum levels. CONCLUSION: In conclusion, we found gender specific differences in Nampt amplitude and coefficient variation with both being higher in females. The circadian rhythm of Nampt was independent of gender in healthy lean individuals, whereas it was disturbed in men with obesity.
Subject(s)
Circadian Rhythm , Cytokines , Exercise , Nicotinamide Phosphoribosyltransferase , Obesity , Humans , Nicotinamide Phosphoribosyltransferase/blood , Male , Female , Circadian Rhythm/physiology , Adult , Obesity/blood , Cytokines/blood , Sex Factors , Exercise/physiology , Body Weight/physiology , Glucose Tolerance Test , Middle Aged , Young AdultABSTRACT
The process of pubertal development is only partly understood and is influenced by many different factors. During the twentieth century there was a general trend toward earlier pubertal development. Fat mass is thought to be a major inducer of puberty. Owing to the rising epidemic of childhood obesity, the relationship between body composition in children and the rate and timing of puberty needs to be investigated. Some studies suggest that central obesity is associated with an earlier onset of pubertal development. Rapid weight gain in early life is linked to advanced puberty in both sexes. A clear correlation exists between increasing body mass index (BMI) and earlier pubertal development in girls. In boys the data are controversial: The majority of studies propose that there is an earlier puberty and voice break in obese boys, but some studies show the opposite. There are several factors and mechanisms that seem to link obesity and puberty, for example, leptin, adipocytokines, and gut peptides. Important players include genetic variation and environmental factors (e.g., endocrine-disrupting chemicals). This article presents the latest studies and evidence on this topic, underlining the inconsistencies in the data and, therefore, the need for further research in this area.
Subject(s)
Disorders of Sex Development/etiology , Disorders of Sex Development/physiopathology , Evidence-Based Medicine , Pediatric Obesity/complications , Pediatric Obesity/physiopathology , Puberty , Sexual Development , Adolescent , Child , Female , Humans , MaleSubject(s)
Carcinoma/diagnosis , Graves Disease/diagnosis , Thyroid Neoplasms/diagnosis , Adolescent , Carcinoma/pathology , Carcinoma/surgery , Carcinoma, Papillary , Combined Modality Therapy , Female , Graves Disease/pathology , Graves Disease/surgery , Humans , Lymph Node Excision , Lymphatic Metastasis/pathology , Reoperation , Thyroid Cancer, Papillary , Thyroid Function Tests , Thyroid Gland/pathology , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroid Nodule/diagnosis , Thyroid Nodule/pathology , Thyroid Nodule/surgery , Thyroidectomy , Triiodothyronine/therapeutic useABSTRACT
Adequate androgen receptor (AR) function is crucial for male sex development and maintenance of secondary male characteristics. Mutations in the AR lead to androgen insensitivity syndrome (AIS) characterized by an end-organ resistance to androgens. The clinical appearance of individuals with 46,XY karyotype and an AR mutation varies widely from normal male to the ultimate completely female phenotype of complete androgen insensitivity syndrome (CAIS). We have analyzed the androgen receptor missense mutations P723S, P904S, and H917R, clinically associated with CAIS, which were described to have a normal maximum androgen binding (Bmax) but elevated equilibrium dissociation constants (Kd's) and compared their properties with the F916X deletion mutant, leading to the loss of the last four amino acids of the AR. Functional analysis allowed a quantitative and qualitative discrimination of these mutants in transactivation, amino-terminal/carboxy-terminal (N/C)-interaction, and coactivation capacity, varying widely with each distinct mutation. We conclude that mutations in the AR have to be characterized meticulously, not only to prove any quantitative functional deficit as a proof of consequence, but also to gain knowledge on qualitative functional properties. This is necessary as a possible link to genotype-phenotype correlation in AIS, but also with respect to medical decision making in CAIS.