Liraglutide treatment counteracts alterations in adipose tissue metabolism induced by orchiectomy in rats

Abstract Aims The reduction in androgens serum concentration is a physiological condition that accompanies age advancement but can also occur because of prostate cancer and gender affirming treatment or pathological conditions such as functional hypogonadism. However, androgen deficiency is related to a higher risk of developing metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). Considering that glucagon-like peptide 1 (GLP1) analogs are increasingly used in the treatment of T2DM, we investigated if liraglutide could also attenuate the metabolic changes caused by orchiectomy in rats. Main methods Wistar rats were orchiectomized (ORC), and subdivided in four groups: sham saline, sham liraglutide, ORC saline, and ORC liraglutide. After sixty days, metabolic parameters were evaluated in blood, muscle, liver, brown (BAT) and white adipose tissue (WAT) visceral depots. Glucose utilization, oxidation, and conversion to lipids by de novo lipogenesis, and basal and adrenaline-stimulated lipolysis were evaluated in BAT and WAT depots. Key findings Orchiectomy increased triglyceridemia, BAT and rtWAT weight, and lipolysis and reduced glucose utilization. Liraglutide treatment reversed these effects. Significance These results indicate that liraglutide improves triglyceridemia and glucose metabolism in WAT depots, which suggests that it may be a promising therapeutic strategy to handle disruptions in energy metabolism caused by androgen deficiency.