Downregulation of chemerin and alleviation of endoplasmic reticulum stress by metformin in adipose tissue of rats

Aims: To investigate whether metformin regulates chemerin expression in vivo by alleviating ER stress. Methods: Male Sprague-Dawley rats were fed a high-fat or normal diet for 10 weeks to induce insulin resistance. During the following 6 weeks, the rats were divided into four groups: normal diet without treatment (NC), normal diet with metformin treatment (NM), high-fat diet without metformin (HF), and high-fat diet with metformin (HM). Body weight, fasting glucose, basal insulin level, insulin sensitivity, chemerin expression in serum and adipose tissue, ER stress marker and its pathway were measured. Results: After 6 weeks treatment, metformin reduced the body weight gain and enhanced insulin sensitivity of high-fat fed rats. The basal insulin level in the HM group was lower than in the HF group. Metformin reduced chemerin expression in the HM group compared with HF. Metformin reduced the GRP78 mRNA expression in HM rats. Activation of IRE1 alpha was lower in the HM group than the HF group. Conclusions: Metformin treatment decreased the chemerin expression and alleviated the ER stress in the visceral adipose tissue of high-fat diet-induced insulin-resistant rats. These data may also provide a further rationale for exploring the use of metformin in the treatment of insulin resistance. (C) 2012 Elsevier Ireland Ltd. All rights reserved.