Multiple hormones controlling energy homeostasis regulate the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Nevertheless, inactivation of the genes encoding NPY and/or AgRP has no impact on food intake in mice. Here we demonstrate that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis.

METHOD:We analyzed data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R and K656N) of LEPR with body mass index (BMI; kg=m 2 ) and waist circumference (WC). A total of 3263 related and unrelated subjects from diverse ethnic backgrounds including African-American, Caucasian, Danish, Finnish, French Canadian and Nigerian were studied. We tested effects of individual alleles, joint effects of alleles at multiple loci, epistatic effects among alleles at different loci, effect modification by age, sex, diabetes and ethnicity, and pleiotropic genotype effects on BMI and WC. RESULTS: We found that none of the effects were significant at the 0.05 level. Heterogeneity tests showed that the variations of the non-significant effects are within the range of sampling variation. CONCLUSION: We conclude that, although certain genotypic effects could be population-specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or WC in the overall population.

Surfactant protein D (SFTPD) belongs to the family of collectins and is part of the innate immune system. Thereby it plays an important role in the defense of various pathogens. Besides it is involved in the development of acute and chronic inflammation of the lung. Levels of SFTPD are elevated in serum and alveolar lavage of asthmatic patients. As SFTPD binds and neutralizes common allergens like house dust mites it is especially important in allergic asthma. Three common amino acid variants have been identified in SFTPD and association of the first variant has been described to severe infection with respiratory syncytial virus. Furthermore the functional impact of all three amino acid variants has been demonstrated. Due to its function SFTPD represents an ideal candidate gene for bronchial asthma and we were interested whether the polymorphisms were in association with asthma in children. The three polymorphisms leading to amino acid exchanges (Met11Thr, Ala160Thr, and Ser270 Thr) were typed by restriction fragment length polymorphisms in 322 asthmatic children and 270 controls. Association analyses were performed by Armitage's trend test. In addition haplotypes were calculated by FASTEHPLUS and FAMHAP. None of the polymorphisms was in association with bronchial asthma. Haplotype analyses revealed four major haplotypes all of which were evenly distributed between the populations. We conclude from our data that functional amino acid variants in SFTPD do not play a major role in the genetic pre-disposition to bronchial asthma in children.