Multifaceted Clinical Research on Obesity-related Disease Prevention Focusing on the DsbA-L Gene

Disulfide bond A oxidoreductase-like protein (DsbA-L) is a protein (previously named glutathione S-transferase kappa 1) found primarily in peroxisomes and mitochondria. DsbA-L is a key molecule in the multimer formation of adiponectin (APN), which has anti-obesity and anti-inflammatory properties. In humans, DsbA-L mRNA levels in adipocytes were reported to be negatively correlated with the body mass index (BMI). Therefore, we focused on the clinical significance of the DsbA-L gene in obesity and obesity-related diseases in Japanese subjects. First, we showed that the DsbA-L rs1917760 polymorphism is associated with APN multimerization and a high BMI among participants of the health screening program and that this polymorphism is indirectly associated with non-alcoholic fatty liver disease. Second, we showed that the DsbA-L rs1917760 polymorphism was associated with a reduction in the respiratory function and with the elevation of the prevalence of airway obstruction among participants of a health screening program. Finally, we showed in a randomized, double-blind, placebo-controlled clinical trial among healthy volunteers that melinjo seed extract promotes APN multimerization, with a greater association in subjects with the DsbA-L rs1917760 T allele. Through these efforts, we showed that DsbA-L is an important molecule associated with obesity and obesity-related diseases and that it may be a useful target for the treatment or prevention of these diseases.