Liraglutide reduces body weight by upregulation of adenylate cyclase 3

Abstract

Objective:According to recent studies, adenylate cyclase 3 (AC3) is associated with obesity. Liraglutide reduces blood glucose levels and body weight (BW). We performed a 2 × 2 factorial experiment to study the relationships among AC3, liraglutide and obesity and to obtain a more comprehensive understanding of the mechanisms underlying the physiological effects of liraglutide on obesity.Methods:A high-fat diet was used to induce obesity in C57BL/6J mice. Both the normal and obese mice were treated with liraglutide (1 mg kg−1) or saline twice daily for 8 weeks. The hepatic levels of the AC3 and glucagon-like peptide receptor (GLP-1R) mRNAs and proteins were measured by quantitative real-time PCR and western blotting, respectively. The serum AC3 levels were detected using a rat/mouse AC3 enzyme-linked immunosorbent assay kit.Results:The administration of liraglutide significantly decreased the BW in obese mice and normal control mice. The BW of obese mice exhibited a more obvious decrease. Hepatic AC3 mRNA and protein levels and serum AC3 levels were significantly reduced in obese mice compared with those in normal control mice. The administration of liraglutide significantly increased the hepatic expression of the AC3 and GLP-1R mRNAs and proteins and serum AC3 levels. The hepatic expression of the AC3 mRNA and protein and serum AC3 levels were negatively correlated with BW loss in the liraglutide-treated group. Pearson’s correlation coefficients for these comparisons are r=−0.448, P=0.048; r=−0.478, P=0.046; and r=−0.909, P=0.000, respectively.Conclusions:Based on our research, liraglutide reduces BW, possibly by increasing the expression of AC3.

Olfactory receptor 10J5 responding to α-cedrene regulates hepatic steatosis via the cAMP–PKA pathway

“…5f ), indicating that α-cedrene affects the protein expression of Adcy3 and PKA Cα in an OR10J5-dependent manner. This finding is in line with the recent reports indicating that protein levels of Adcy3 36 , 37 and PKA Cα 38 was upregulated in response to agonist-induced stimulation of a GPCR in mouse liver tissue and bone marrow stromal cells, respectively. Nevertheless, it remains to be determined how α-cedrene that acts through OR10J5 impacts Adcy3 and PKA Cα expression.…”

Genetics of metabolic traits in Greenlanders: lessons from an isolated population

“…Interestingly, treatment with a GLP‐1R agonist, prescribed to improve glycaemic control in patients with type 2 diabetes, leads to reduced body weight and reduced insulin resistance combined with up‐regulated hepatic levels of Adcy3 mRNA and protein in diabesity and obese mice . These observations fit with the observation of weight‐reducing properties of GLP‐1R‐agonist treatment in patients with type 2 diabetes , which thus might be explained, at least partly, by ADCY3 activation.…”

Dual Therapy with Liraglutide and Ghrelin Promotes Brain and Peripheral Energy Metabolism in the R6/2 Mouse Model of Huntington’s Disease

“…We recently showed that chronic ghrelin administration for 4 weeks postpones R6/2 mouse weight loss by one week 38 . Administration of the GLP-1 analogue, liraglutide, has been shown to be associated with weight loss 22 , 39 , which could be problematic if used in a mouse model displaying weight loss, such as the R6/2 mouse. However, we here demonstrate that daily injections of either liraglutide alone or together with ghrelin for 2 weeks (from 10 to 12 weeks of age) did not further decrease body weight in R6/2 mice.…”