Stratified analysis of lectin-like chaperones in the folding disease-related metabolic syndrome rat model

• Published in: Biochemical and biophysical research communications 2016-09, Vol.478 (1), p.247-253
• Main Authors: Hirano, Makoto, Imagawa, Ayami, Totani, Kiichiro
• Format: Article
• Language: English
• Subjects: Aggregation; Animals; Calnexin - metabolism; Calreticulin - metabolism; Chaperone; Diabetes mellitus; Endoplasmic reticulum; Lectins - metabolism; Male; Metabolic Syndrome - metabolism; Molecular Chaperones - metabolism; Obesity; Obesity - metabolism; Protein Folding; Protein interaction; Proteostasis Deficiencies - metabolism; Rats; Rats, Zucker
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.07.060

The metabolic syndrome including obesity and diabetes mellitus is known to be a major health problem worldwide. A recent study reported that obesity causes endoplasmic reticulum (ER) stress and subsequently leads to insulin resistance and type 2 diabetes. However, little is known about the alterations in the components of the calnexin/calreticulin (CNX/CRT) cycle, which promote glycoprotein folding in obese and diabetic conditions. To understand the operating status of the lectin-like chaperones related to the CNX/CRT cycle in the metabolic syndrome, we analyzed the chaperones for the activity, protein expression, and mRNA expression levels using Zucker fatty (ZF) and Zucker diabetic fatty (ZDF) rat models for obesity and diabetes, respectively. We demonstrated that misfolded proteins were gradually increased with progression of the syndrome, obesity to diabetes. The individual chaperone activities of CNX and CRT were both decreased in the ZF rat ER and, in contrast, were increased in the ZDF rat ER. The protein quantities and mRNA expressions of CNX and CRT were decreased in the ZF rats, but increased in the ZDF rats compared with those of the healthy model. Therefore, these results indicate that obesity down-regulates CNX and CRT expressions and their activities and diabetes up-regulates the expressions and activities of CNX and CRT. Our findings clearly suggest that metabolic syndrome affects the lectin-like chaperones in the CNX/CRT cycle at both the activity and expression levels. •Misfolded proteins were accumulated according to the severity of metabolic syndrome.•The activities of calnexin (CNX) and calreticulin (CRT) were decreased in obese rats.•CNX and CRT activities were increased in diabetic rats compared with healthy rats.•Obesity down-regulated CNX and CRT expressions.•Diabetes up-regulated CNX and CRT expressions compared with healthy conditions.