肥満解消のための無作為介入研究による脂肪量とアディポサイトカインの変化

Adipocytokines arebioactive substances synthesizedand secretedbyfat cell. Previous studies have reported an association between weight loss and adipocytokines. However, these studies are inconsistent and they have not clarified the relationship between weight regain and changes in circulating levels of adipocytokines. In this study, we analyzed the relationship between weight and fat volume changes and adipocytokines. The subjects were 235obese people recruited in the Saku Control Obesity Program (SCOP). Participants were randomly assigned to either immediate (Group A) or delayed (Group B, control group). Group A participants were followed for another two years after completion of the one year intervention. As controls, Group B participants received the same intervention as Group A after a delay of one year. Then they were followed up for one year. The intervention consisted in a one-year lifestyle program to induce weight loss, based on a cognitive-behavioral approach. After the first year of the study, body weight, BMI, body fat and abdominal fat areas were significantly lower in group A participants, compared to controls. After the intervention, leptin levels were significantly lowered both in men and women. After one year follow-up, both men and women re-gained about 1.5 kg body weight on average. BMI, waist circumference, fat areas by CT and HBA1c significantly increased during the follow-up period. The change of adipocytokine levels by analysis of the quartile of body weight decrease and regain revealed that increased adiponectin and decreased leptin was noteworthy for weight reduction, while increase of leptin influenced the weight regain. In conclusion, our results suggest that leptin could have broad effects on the distribution off at tissues and on lipid metabolism. Leptin inversely associated with adiponectin, which in turn was necessary to decrease body weight. In particular, leptin decreased remarkably in the process of weight reduction, and its increase seemed to be related in weight regain. The observed increase of adiponectin seemed to be induced by reduction in fat volume

Common Variants in the COL4A4 Gene Confer Susceptibility to Lattice Degeneration of the Retina

Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS) using a dense panel of 23,465 microsatellite markers covering the entire human genome. This GWAS in a Japanese cohort (294 patients with lattice degeneration and 294 controls) led to the identification of one microsatellite locus, D2S0276i, in the collagen type IV alpha 4 (COL4A4) gene on chromosome 2q36.3. To validate the significance of this observation, we evaluated the D2S0276i region in the GWAS cohort and in an independent Japanese cohort (280 patients and 314 controls) using D2S0276i and 47 single nucleotide polymorphisms covering the region. The strong associations were observed in D2S0276i and rs7558081 in the COL4A4 gene (Pc = 5.8×10−6, OR = 0.63 and Pc = 1.0×10−5, OR = 0.69 in a total of 574 patients and 608 controls, respectively). Our findings suggest that variants in the COL4A4 gene may contribute to the development of lattice degeneration of the retina

Heparan sulfate in the tumor microenvironment

The biology of tumor cells strictly depends on their microenvironment architecture and composition, which controls the availability of growth factors and signaling molecules. Thus, the network of glycosaminoglycans, proteoglycans, and proteins known as extracellular matrix (ECM) that surrounds the cells plays a central role in the regulation of tumor fate. Heparan sulfate (HS) and heparan sulfate proteoglycans (HSPGs) are highly versatile ECM components that bind and regulate the activity of growth factors, cell membrane receptors, and other ECM molecules. These HS binding partners modulate cell adhesion, motility, and proliferation that are processes altered during tumor progression. Modification in the expression and activity of HS, HSPGs, and the respective metabolic enzymes results unavoidably in alteration of tumor cell microenvironment. In this light, the targeting of HS structure and metabolism is potentially a new tool in the treatment of different cancer types