Objective To examine the relationship of 5-amino levulinic acid (5-ALA) with endoplasmic reticulum stress and glucose metabolism and potential related molecular mechanisms.
Methods Ten C57BL/6J mice at eight weeks of age were induced to establish obese mice model by 16-week high fat diet after one week of adaptive feeding, then randomly divided into an 5-ALA group5 mg/(kg& #183;d) and a control groupphosphate buffered saline 1 mL/(kg& #183;d), for nine consecutive weeks. During the intragastric administration, blood samples were collected from tail vein after 12 h of fasting for measuring fasting blood glucose levels. Nine weeks later, the mice liver and epididymal adipose tissues were separated to extract RNA and protein and measure the expressions of C/EBP homologous protein (CHOP), X-box binding protein 1s (XBP-1s), binding immunoglobulin protein (BiP), and endoplasmic reticulum DnaJ protein family member 4 (ERdj4).
Results Compared with the control group(6.54& #177;0.05)mmol/L, the fasting blood glucose levels in the mice treated with 5-ALA were lowered from week 5(6.40& #177;0.35) mmol/L with little variation and showed a significant decrease at week 7(6.02& #177;0.17) mmol/L (P < 0.05). The real-time polymerase chain reaction results showed that 5-ALA significantly inhibited the increased mRNA levels of XBP-1s induced by obesity (2-△△CT for the 5-ALA group was 0.029& #177;0.017, 2-△△CT for the control group was 0.029& #177;0.006, P < 0.05). The western blotting results indicated that the expression of XBP-1s was lower in the 5-ALA group than in the control group.
Conclusion 5-ALA could improve glucose metabolism in mice by inhibiting endoplasmic reticulum stress via IRE1-XBP-1 pathway in white adipose tissues.