The DLK1 human gene encodes for the transmembrane EGF-like repeat-containing protein DLK1, which acts as a modulator of adipogenesis. A role for DLK1 in energy metabolism and lipid homeostasis has bee Show more
The DLK1 human gene encodes for the transmembrane EGF-like repeat-containing protein DLK1, which acts as a modulator of adipogenesis. A role for DLK1 in energy metabolism and lipid homeostasis has been suggested and DLK1 gene variants have been related to pubertal development. The aim of this study was to uncover DLK1 SNPs in a cohort of children and analyze their relationship with anthropometric and biochemical variables. Our population-based sample comprises 1237 healthy 6-to-8-year-old Caucasian children. The presence of five DLK1 SNPs (rs1802710, rs876374, rs7155375, rs57098752, and rs7149242) was analyzed by Real-Time PCR, using predesigned TaqMan™ Genotyping Assays. We observed that the SNPs rs1802710 and rs876374 were associated with BMI, and the prevalence of these two SNPs was different in normal-weight children compared to children with obesity. Related to biochemical variables, we found a significant association of the SNPs rs1802710, rs876374, and rs57098752 and their combination with Apo-B plasma concentrations after adjusting by BMI and sex. The SNPs rs1802710 and rs57098752 were also significantly associated with plasma levels of LDL-C and HDL-C, respectively. Our study reveals that DLK1 gene variants may influence both body weight and lipid homeostasis, affecting particularly to the Apo-B biology, in children. DLK1 polymorphisms are associated with BMI and with lipid levels, independently of BMI, early in life. Our data add to the existing literature the evidence that DLK1 gene variants impact on lipid metabolism. The confirmation at the population level that DLK1 genetic variants are associated with anthropometric and lipid variables sustains the role of DLK1 in obesity and related disorders and should lead to further studies aimed at clarifying this effect. Show less
Recent studies have associated alterations of neuronal plasticity in specific brain areas with suicidal behavior. The Notch signaling pathway plays a relevant role in the control of stem cell maintena Show more
Recent studies have associated alterations of neuronal plasticity in specific brain areas with suicidal behavior. The Notch signaling pathway plays a relevant role in the control of stem cell maintenance, cell migration, and neuronal plasticity. In the present study, the gene expression of the four Notch receptors (NOTCH1-4), the five canonical ligands (DLL1, DLL3, DLL4, JAGGED1, and JAGGED2), the two non-canonical ligands (DLK1 and DLK2), and the transcription factors (HES1, HEY1, and HEY2) were measured in the dorsolateral prefrontal cortex (DLPFC) and amygdala (AMY) of suicide victims (S; n = 13 males, with no clinical psychiatric history and non-treated with anxiolytic or antidepressant drugs) and their corresponding controls (C; n = 13 males) by real-time PCR. The results revealed a reduction of NOTCH2 and NOTCH1, NOTCH3, and NOTCH4 gene expression in the DLPFC and AMY of S compared with C, respectively. DLL1 levels were increased in the DLPFC and decreased in the AMY, whereas DLL4, JAGGED1, and JAGGED2 were significantly decreased in the regions analyzed. DLK1 was reduced in the AMY, whereas no changes were observed in the DLPFC and in DLK2 expression levels in any of the regions analyzed. HES1 was significantly reduced in both brain regions from S, whereas there were no significant changes in HEY1 and HEY2. This study provides evidence suggesting that the Notch signaling pathway could be a potential key target in the treatment of suicidal behaviors. Show less