Parent-related mechanisms underlying the social gradient of childhood overweight and obesity: a systematic review.

BACKGROUND: Low socio-economic status (SES) is a significant risk factor for childhood overweight and obesity (COWOB) in high-income countries. Parents to young children buffer and accentuate social and cultural influences, and are central to the development of this disease. An understanding of the parent-related mechanisms that underlie the SES-COWOB relationship is needed to improve the efficacy of prevention and intervention efforts. OBJECTIVE: A systematic review of relevant literature was conducted to investigate the mechanisms by which levels of SES (low, middle and high) are associated to COWOB, by exploring mediation and interaction effects. METHOD: Six electronic databases were searched yielding 5155 initial records, once duplicates were removed. Studies were included if they investigated COWOB, SES, parent-related factors and the multivariate relationship between these factors. Thirty studies were included. Factors found to be mediating the SES-COWOB relationship or interacting with SES to influence COWOB were categorized according to an ecological systems framework, at child, parent, household and social system level factors. RESULTS: High parent body mass index, ethnicity, child-care attendance, high TV time (mother and child), breastfeeding (early weaning), food intake behaviours and birthweight potentially mediate the relationship between SES and COWOB. Different risk factors for COWOB in different SES groups were found. For low SES families, parental obesity and maternal depressive symptoms were strong risk factors for COWOB, whereas long maternal working hours and a permissive parenting style were risk factors for higher SES families. None of the studies investigated parental psychological attributes such as attitudes, beliefs, self-esteem and so on as potential mechanisms/risk factors. CONCLUSIONS: Families from different SES groups have different risk and protective factors for COWOB. Prevention and intervention efforts may have improved efficacy if they are tailored to address specific risk factors within SES.

The death associated protein (DAP) kinase homologue Dlk/ZIP kinase induces p19ARF- and p53-independent apoptosis.

Dlk/ZIP kinase is one of five members of the death associated protein (DAP) kinase family. DAP kinase is able to induce apoptosis in a p19ARF/p53-dependent manner. We elucidated the potential role of the p19ARF/p53 pathway in Dlk/ZIP kinase-triggered cell death. Overexpression of a constitutively pro-apoptotic form of Dlk/ZIP kinase induced apoptosis in rat fibroblast cells which express wild-type p19ARF and p53. Cell death was characterised by apoptotic membrane blebbing, mitochondrial depolarisation, cytochrome c release and activation of caspase-3. However, Dlk/ZIP kinase-triggered cell death was also observed in p19ARF-deficient and p53-deficient mouse fibroblast cells. Quantitative analysis revealed that the status of p53 had no major influence on cellular susceptibility to Dlk/ZIP kinase-triggered cell death. Loss of p53 did not prevent Dlk/ZIP kinase-induced mitochondrial membrane depolarisation and release of cytochrome c. Furthermore, overexpression of Dlk/ZIP kinase did not lead to an increased expression of pro-apoptotic p53 target genes in either cell line. These data suggest that Dlk/ZIP kinase is able to trigger the mitochondrial apoptosis pathway independent of the p19ARF/p53 signalling pathway.

Dlk/ZIP kinase-induced apoptosis in human medulloblastoma cells: requirement of the mitochondrial apoptosis pathway.

Dlk/ZIP kinase is a member of the Death Associated Protein (DAP) kinase family of pro-apoptotic serine/threonine kinases that have been implicated in regulation of apoptosis and tumour suppression. Expression of both Dlk/ZIP kinase and its interaction partner Par-4 is maintained in four medulloblastoma cell lines investigated, whereas three of seven neuroblastoma cell lines have lost expression of Par-4. Overexpression of a constitutively pro-apoptotic deletion mutant of Dlk/ZIP kinase induced significant apoptosis in D283 medulloblastoma cells. Cell death was characterized by apoptotic membrane blebbing, and a late stage during which the cells had ceased blebbing and were drastically shrunken or disrupted into apoptotic bodies. Over-expression of the anti-apoptotic Bcl-xL protein had no effect on Dlk/ZIP kinase-induced membrane blebbing, but potently inhibited Dlk/ZIP kinase-induced cytochrome c release and transition of cells to late stage apoptosis. Treatment with caspase inhibitors delayed, but did not prevent entry into late stage apoptosis. These results demonstrate that Dlk/ZIP kinase-triggered apoptosis involves the mitochondrial apoptosis pathway. However, cell death proceeded in the presence of caspase inhibitors, suggesting that Dlk/ZIP kinase is able to activate alternative cell death pathways. Alterations of signal transduction pathways leading to Dlk/ZIP kinase induced apoptosis or loss of expression of upstream activators could play important roles in tumour progression and metastasis of neural tumours.