The Effect Of High-Fat Diet On Adipose Tissue Glycerol Metabolism Is Influenced By Sex And Glp-1 Agonist Treatment

During fasting triglyceride (TG) in adipose tissue (AT) is hydrolyzed into fatty acids and glycerol. Glycerol exits AT through the glycerol channel aquaporin 7 (AQP7). AQP7 KO mice have increased activity of AT glycerol kinase (GlyK), increased storage of TG, and become obese indicating that changes in AT glycerol metabolism influences TG storage. Moreover, in humans an association between low expression of AQP7 and obesity has been found in women only. This study aims to investigate whether high fat diet (HFD) influences AT glycerol metabolism in a sex-specific manner and whether the glycerol metabolism is influenced by GLP-1 agonist treatment. Female and male C57BL/6J mice (10 weeks) were fed a control diet or HFD for 12 or 24 weeks. The GLP-1 agonist Liraglutide was administered (SC, 1 mg/kg/day) to a subgroup of control and HFD fed female mice during the last 12 of the 24 weeks. Body weight (BW) and blood glucose (BG) were monitored and the expression of AQP7, GlyK, and lipolytic enzymes were investigated using immunoblotting of perigonadal AT and analyzed using Two-Way ANOVA. After 12 weeks, HFD increased BW by 34% in female and by 49% in male mice. BG levels were significantly increased in male mice only. After 24 weeks, HFD increased BW by 76% in female and by 49% in male mice and BG levels was significantly increased in both sexes. Liraglutide decreased both BW and BG levels compared to untreated controls. HFD increased the expression of AQP7 in female mice only and after 24 weeks of HFD this was paralleled by a more than 4-fold increase in GlyK and a 50% reduction in adipose triglyceride lipase abundance (ATGL). Liraglutide treatment normalized the expression of both AQP7 and GlyK. In male mice the abundance of GlyK was increased after 12 and 24 weeks of HFD. In conclusion, HFD influences the expression of AQP7 in AT in a sex-specific manner. The increase in GlyK suggests an increased utilization of glycerol for TG synthesis in both sexes. Liraglutide treatment influences AT glycerol metabolism. Disclosure F.M. Iena: None. J. Vegger: None. J. Thomsen: None. A. Brüel: None. J. Lebeck: None. Funding Aarhus University