Melinjo seed extract (MSe) contains large amounts of polyphenols, including dimers of trans-resveratrol (e.g. gnetin c, L, gnemonoside A, B and D), and has been shown to potentially improve obesity. However, there is no clinical evidence regarding the anti-obesity effects of MSE, and its mechanisms are also unclear. We investigated the hypothesis that MSe supplementation increases the adiponectin (Apn) multimerization via the up-regulation of disulfide bond A oxidoreductase-like protein (DsbA-L) under either or both physiological and obese conditions. To investigate the effect of MSE on the physiological condition, 42 healthy young volunteers were enrolled in a randomized, double-blind placebo-controlled clinical trial for 14 days. The participants were randomly assigned to the MSE 150 mg/day, MSE 300 mg/day or placebo groups. Furthermore, in order to investigate the effect of MSE on APN levels under obese conditions, we administered MSE powder (500 or 1000 mg/kg/day) to control-diet-or high-fat-diet (HFD)-fed C57BL/6 mice for 4 weeks. All participants completed the clinical trial. The administration of MSE 300 mg/day was associated with an increase in the ratio of HMW/ total Apn in relation to the genes regulating Apn multimerization, including DsbA-L. furthermore, this effect of MSE was more pronounced in carriers of the DsbA-L rs191776 G/T or T/T genotype than in others. in addition, the administration of MSe to HfD mice suppressed their metabolic abnormalities (i.e. weight gain, increased blood glucose level and fat mass accumulation) and increased the levels of total and HMW Apn in serum and the mRnA levels of ADIPOQ and DsbA-L in adipose tissue. the present study suggests that MSE may exert beneficial effects via Apn multimerization in relation to the induction of DsbA-L under both physiological and obese conditions. Melinjo (Gnetum gnemon L.) is a gymnosperm native of Indonesia, and its seeds have long been eaten by the people of Indonesia 1. Melinjo seed extract (MSE) contains large amounts of polyphenols, including trans-resveratrol, gnetin C (dimer of trans-resveratrol), gnemonoside A (di-glucoside from gnetin C) and gnemonoside D (mono-glucoside from gnetin C), gnemonoside C (mono-glycoside from gnetin C) and gnetin L (derivative of gnetin C) 1. Resveratrols, in particular trans-resveratrol, have been reported to have diverse health benefits, demonstrating utility for treating aging-related diseases, including cancer, cardiovascular disease, type 2 diabetes and neurodegenerative disease in animal studies 2-4 ; however, its health benefits in humans are still controversial. One reason for this lack of certainty regarding its effects may be the rapid and presystemic metabolism of

The patatin-like phospholipase domain containing protein 3 (PNPLA3) rs738409 polymorphism (c.444C>G) is the most well-known genetic risk factor for non-alcoholic fatty liver disease (NAFLD), but whether or not physical activity influences the association between the PNPLA3 genotype and risk of NAFLD is unclear. Patients and Methods: A retrospective longitudinal analysis was conducted among 352 Japanese subjects. Each type of physical activity was assigned a metabolic equivalent (MET), and the subjects were classified into sedentary, low or high groups using the "METS*T" (METs × hours per week) value of 5 or 21 as a threshold. Results: Among the PNPLA3 G/G genotype carriers, the high and low METS*T groups had a lower risk of NAFLD than the sedentary METS*T group (odds ratio [95% confidence interval]: 0.14 [0.02-0.99] and 0.16 [0.03-1.04], respectively). Furthermore, the PNPLA3 C/C or C/G genotype carriers showed no significant difference in the risk of NAFLD among the three METS*T groups. Conclusion: The PNPLA3 rs738409 genotype may be associated with the beneficial effects of physical activity on the risk of NAFLD among elderly Japanese individuals. Further comprehensive investigations are therefore needed to verify the preliminary results.

Oxidative stress and inflammation play a key role in the age-related decline in the respiratory function. Adipokine in relation to the metabolic and inflammatory systems is attracting growing interest in the field of respiratory dysfunction. The present clinical and experimental studies investigated the role of the disulfide bond-forming oxidoreductase Alike protein (DsbA-L) gene, which has antioxidant and adiponectin multimeric (i.e. activation) properties, on the respiratory function of the elderly. We performed a retrospective longitudinal genotype-phenotype relationship analysis of 318 Japanese relatively elderly participants (mean age ± standard deviation: 67.0 ± 5.8 years) during a health screening program and an in vitro DsbA-L knock-down evaluation using 16HBE14o-cells, a commonly evaluated human airway epithelial cell line. The DsbA-L rs1917760 polymorphism was associated with a reduction in the ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) and %FEV1 and with the elevation of the prevalence of FEV1/FVC < 70%. We also confirmed that the polymorphism was associated with a decreased respiratory function in relation to a decrease in the ratio of high-molecular-weight adiponectin/total adiponectin (as a marker of adiponectin multimerization) and an increase in the oxidized human serum albumin (as an oxidative stress marker). Furthermore, we clarified that DsbA-L knock-down induced oxidative stress and up-regulated the mucus production in human airway epithelial cells. These findings suggest that the DsbA-L gene may play a role in protecting the respiratory function of the elderly, possibly via increased systemic adiponectin functions secreted from adipocytes or through systemic and/or local pulmonary antioxidant properties. Airway inflammation and an impaired lung function are common in elderly populations, leading to decreased quality of life and increase in morbidity and mortality 1-3. Although exposures to cigarette smoke and other environmental pollutants (e.g. biomass fuel exposure and air pollution) are major risk factors for the development and progression of respiratory dysfunction 4,5 , previous evidence has shown that age-related changes in the respiratory functions are also key factors for respiratory dysfunction 1-3. Aging causes the loss of lung elasticity, decreased respiratory muscles, and a decreased surface area for alveolar gas exchange, leading to an impaired respiratory function 1-3. Furthermore, local and/or systemic oxidative stress as well as inflammation play substantial roles in the age-related decline in the respiratory function 1,2. However, these changes in respiratory pathological features