Systemic overexpression of the 11β‑HSD1 promotes endoplasmic reticulum stress in multiple tissues and the development of metabolic syndrome in mice.

Glucocorticoids are associated with lipid metabolism and their abnormal expression has an important function in the development of metabolic syndrome. The 11β‑hydroxysteroid dehydrogenase type 1 (11β‑HSD1) is a metabolic enzyme of glucocorticoids and may be a potential drug target for the treatment of metabolic syndrome. However, the association between the systemic expression of 11β‑HSD1 and metabolic syndrome remains to be elucidated. The present study used a cytomegalovirus promoter to obtain mice that systemically overexpressed the 11β‑HSD1 gene. The transgenic mice and negative control groups received a high‑fat diet at the age of 10 weeks in order to induce metabolic syndrome and this diet was continued for 12 weeks. Several indicators, including body weight, blood glucose, glucose tolerance and insulin resistance, were monitored in vivo. In addition, the protein expression levels of 11β‑HSD1 and DNA damage inducible transcript 3 were detected and the histopathology of important tissues for metabolic syndrome were analyzed. The current findings revealed that the body weights of transgenic mice were significantly higher compared with the control group before and during the periods of high fat diet induction. Transgenic mice also exhibited significantly impaired glucose tolerance, insulin resistance, endoplasmic reticulum stress and increased metabolic syndrome‑associated biochemical indicators in the blood and severely impaired liver and kidney functions. The present study successfully established a 11β‑HSD1 systemic overexpression mouse model that exhibited typical characteristics of metabolic syndrome and may be useful for future studies of metabolic syndrome.