Mirtazapine Reduces Adipocyte Hypertrophy and Increases Glucose Transporter Expression in Obese Mice

SIMPLE SUMMARY: Mirtazapine, a tetracyclic antidepressant, acts through noradrenergic and specific serotonergic systems. Consequently, it was recently applied in major depressive disorder treatment. Moreover, because mirtazapine may have effective glucose control function, its mechanism of action warrants further investigation. In our study, we examined how mirtazapine affects metabolic parameters, insulin profiles, glucose metabolism, and obesity changes in high-fat diet-fed C57BL6/J mice. Our results indicated that compared with untreated mice, mirtazapine-treated obese mice had lower insulin levels, daily food efficiency, body weight, serum triglyceride levels, aspartate aminotransferase levels, liver and epididymal fat pad weight, and fatty acid regulation marker expression. Moreover, the blood glucose levels and area under the curve for glucose levels observed over a 120 min assessment period were lower in the treated mice, but the insulin sensitivity and glucose transporter 4 expression levels were higher in these mice. They also demonstrated a considerable decrease in fatty liver scores and mean fat cell size in the epididymal white adipose tissue, paralleling adenosine monophosphate (AMP)-activated protein kinase expression activation. In conclusion, mirtazapine administration may alleviate type 2 diabetes mellitus with hyperglycemia. ABSTRACT: Metabolic syndrome is known to engender type 2 diabetes as well as some cardiac, cerebrovascular, and kidney diseases. Mirtazapine—an atypical second-generation antipsychotic drug with less severe side effects than atypical first-generation antipsychotics—may have positive effects on blood glucose levels and obesity. In our executed study, we treated male high-fat diet (HFD)-fed C57BL/6J mice with mirtazapine (10 mg/kg/day mirtazapine) for 4 weeks to understand its antiobesity effects. We noted these mice to exhibit lower insulin levels, daily food efficiency, body weight, serum triglyceride levels, aspartate aminotransferase levels, liver and epididymal fat pad weight, and fatty acid regulation marker expression when compared with their counterparts (i.e., HFD-fed control mice). Furthermore, we determined a considerable drop in fatty liver scores and mean fat cell size in the epididymal white adipose tissue in the treated mice, corresponding to AMP-activated protein kinase expression activation. Notably, the treated mice showed lower glucose tolerance and blood glucose levels, but higher glucose transporter 4 expression. Overall, the aforementioned findings signify that mirtazapine could reduce lipid accumulation and thus prevent HFD-induced increase in body weight. In conclusion, mirtazapine may be useful in body weight control and antihyperglycemia therapy.