A randomized clinical trial of the effectiveness of a Web-based health behaviour change support system and group lifestyle counselling on body weight loss in overweight and obese subjects: 2-year outcomes.

BACKGROUND: Weight loss can prevent and treat obesity-related diseases. However, lost weight is usually regained, returning to the initial or even higher levels in the long term. New counselling methods for maintaining lifestyle changes are urgently needed. OBJECTIVES: An information and communication technology-based health behaviour change support system (HBCSS) that utilizes persuasive design and methods of cognitive behavioural therapy (CBT) was developed with the aim of helping individuals to maintain body weight. The purpose of this study was to assess whether CBT-based group counselling combined with HBCSS or HBCSS alone helps to maintain improved lifestyle changes needed for weight loss compared to self-help guidance or usual care. METHODS: A randomized lifestyle intervention for overweight or obese persons (BMI 27-35 kg m-2 and age 20-60 years), recruited from the population registry in the city of Oulu, Finland, was conducted. This study comprised six randomly assigned study arms: CBT-based group counselling (eight sessions led by a nutritionist), self-help guidance-based group counselling (SHG; two sessions led by a nurse) and control, each with or without HCBSS, for 52 weeks. Subjects visited the study centre for anthropometric measurements, blood sample collection and to complete questionnaires at baseline, 12 and 24 months. The main outcome was weight change from baseline to 12 months and from baseline to 24 months. RESULTS: Of the 1065 volunteers screened for the study, 532 subjects (51% men) met the inclusion criteria and were enrolled. The retention rate was 80% at 12 months and 70% at 24 months. CBT-based counselling with HBCSS produced the largest weight reduction without any significant weight gain during follow-up. The mean weight change in this arm was 4.1% [95% confidence interval (CI), -5.4 to -2.8, P < 0.001) at 12 months and 3.4% (95% CI, -4.8 to -2.0, P < 0.001) at 24 months. HBCSS even without any group counselling reduced the mean weight by 1.6% (95% CI, -2.9 to -0.3, P = 0.015) at 24 months. CONCLUSION: The combination of CBT-based group counselling and HBCSS-based weight management is feasible for overweight or obese individuals. Moreover, HBCSS alone could be disseminated to the population at large as an effective means of treating obesity.

Programming effects of FTO in the development of obesity.

It is becoming increasingly recognized that early-life nutritional, metabolic and environmental factors can have a long-term impact on the early onset of obesity, type 2 diabetes and cardiovascular diseases. Numerous experimental and epidemiological observations support the concept that an individual's response to their adult lifestyle and nutritional environment depends not only on their genetic susceptibility but also on their previous early-life experiences. The current research challenge is to determine the primary pathways contributing to 'non- or epi-genetic' causes of excess adult weight gain and adiposity. Evidence from the fields of genetic epidemiology, life course modelling and diet-induced foetal programming all support a role for the FTO gene in this complex biological interaction. It may provide a missing link in the developmental regulation of energy metabolism. Our review therefore considers the role of the FTO gene in the early-life determination of body weight, body composition and energy balance. We will summarize current knowledge on FTO biology combining human genetic epidemiology, molecular models and findings from animal studies. Notably, we will focus on the role of FTO in energy balance in humans, the importance of FTO polymorphisms in childhood growth and the impact of foetal nutrition. Ultimately, we propose a new hypothesis for future research designed to understand the role of FTO in setting gene expression in metabolically active tissues.

Alcohol-induced premature permeability in mouse placenta-yolk sac barriers in vivo.

OBJECTIVE: Acute alcohol exposure induces malformation and malfunction of placenta-yolk sac tissues in rodents, reducing the labyrinth zone in the placenta and altering the permeability and fluidity of the cell membrane. During normal mouse placentation the cells line up in an optimal way to form a hemotrichorial placenta where layers II and III are connected through gap junctions. These act as molecular sieves that limit the passage of large molecules. PlGF is a developmentally regulated protein that controls the passage of molecules in the vasculosyncytial membranes and media of large blood vessels in the placental villi. In addition to the chorioallontoic placenta, rodents also have another type of placenta that consists of Reichert's membrane within the trophoblast cell layer on the maternal side and the parietal endodermal cells on the embryonic site. This forms a separate materno-fetal transport system. We study here whether alcohol affects these two placental barriers, leading to placental malfunction that in turn diminishes the nutrient supply to the embryo. STUDY DESIGN: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals at 8.75 days post coitum (dpc). The placentas were collected on 9.5, 11.5 and 14.5 dpc and used for histopathological protein studies. Hemotrichorial cell layer structure interactions through connective tissue and gap junction were analyzed by electron microscopy. The permeability of the feto-maternal barrier was visualized with Evans Blue. RESULTS: VEGF, a permeability inducer, was found to be up-regulated in the mouse placenta after acute alcohol exposure, and permeability was also affected by altered structures in the barriers that separate the feto-maternal blood circulation which destroyed the gap junctions in the hemotrichorial cell layer, reduced the thickness of Reichert's membrane and interfered with with Reichert's trophoblast/Reichert's parietal interaction. These defects together could have caused the permeability malfunction of the placenta-yolk sac tissues as visualized and quantified here by Evans Blue leakage. CONCLUSIONS: An altered PlGF/VEGF ratio together with barrier malformation may contribute to placental malfunction by altering the permeability of the feto-maternal barriers. Further studies are needed in order to show whether premature permeability is involved in the intrauterine growth restriction observed in human FAS embryos.

Closed-circuit organ perfusion technique for gene transfer into the lungs. An experimental trial on farm pigs.

In an attempt to develop gene therapy for lung diseases, we have explored a closed-circuit surgical perfusion method for gene transfer into the lung. For gene transfer we used a replication defective type 5 adenovirus carrying the E. coli beta-galactosidase gene as a reporter gene. The middle lobe of the right lung of eight young farm pigs was perfused in vivo via thoracotomy for up to 60 min with the viral solution. The gene transfer was performed using a closed-circuit organ perfusion method in vivo. The efficiency of gene transfer was assessed visually by analysis of histologic sections after X-gal, PAS and immunohistochemical stainings. The lung perfusion resulted in transgene expression in the alveolar epithelial cells, capillary endothelial cells, airway epithelial cells and alveolar macrophages of the lung examined seven days after perfusion. The present results suggest that operatively performed closed-circuit warm lung perfusion method may be used for gene transfer in treatment of diseases that have pulmonary manifestations.

Murine matrix metalloproteinase 9 gene. 5'-upstream region contains cis-acting elements for expression in osteoclasts and migrating keratinocytes in transgenic mice.

Knowledge about the regulation of cell lineage-specific expression of extracellular matrix metalloproteinases is limited. In the present work, the murine matrix metalloproteinase 9 (MMP-9) gene was shown to contain 13 exons, and the 2.8-kilobase pair upstream region was found to contain several common promoter elements including a TATA box-like motif, three GC boxes, four AP-1-like binding sites, an AP-2 site, and three PEA3 consensus sequences that may be important for basic activity of the gene. In order to identify cell-specific regulatory elements, constructs containing varying lengths of the upstream region in front of a LacZ reporter gene were made and studied for expression in transgenic mice generated by microinjection into fertilized oocytes. Analyses of the mice revealed that the presence of sequences between -2722 and -7745 allowed for expression in osteoclasts and migrating keratinocytes, i. e. cells that have been shown to normally express the enzyme in vivo. The results represent the first in vivo demonstration of the location of cell-specific control elements in a matrix metalloproteinase gene and show that element(s) regulating most cell-specific activities of 92-kDa type collagenase are located in the -2722 to -7745 base pair region.