title: Hepatic adenylate cyclase 3 is upregulated by Liraglutide and subsequently plays a protective role in insulin resistance and obesity.
abstract: OBJECTIVE
  Recent studies have demonstrated that adenylate cyclase 3 (AC3) has a protective role in obesity. This gene resides at the pathway with glucagon-like peptide (GLP)-1. Liraglutide is a GLP-1 analog and has independent glucose and body weight (BW)-reducing effects. In the present study, we aimed to examine whether hepatic AC3 activity was regulated by Liraglutide and to further understand the effect of AC3 in reduction of BW and insulin resistance.
  
  
  METHODS
  The diabesity and obese mice were induced from db/db and C57BL/6 J mice, respectively, by high-fat diet. Liraglutide (0.1 mg kg(-1) per 12 h) was given to the mice twice daily for 12 weeks. C57BL/6 J mice fed with chow diet and obese or diabesity mice treated with saline were used as the controls. Hepatic AC3 gene expression at mRNA and protein levels was analyzed with real-time reverse transcription-PCR and western blot. Fasting blood glucose and serum insulin levels were measured and followed insulin resistance index (HOMA-IR) was evaluated according to the homeostasis model assessment.
  
  
  RESULTS
  After administration of Liraglutide, BW and HOMA-IR in obese and diabesity mice were decreased, whereas hepatic AC3 mRNA and protein expression levels were upregulated. The AC3 gene expression was negatively correlated with BW, HOMA-IR and the area ratio of hepatic fat deposition in the liver.
  
  
  CONCLUSIONS
  The present study thus provides the evidence that hepatic AC3 gene expression is upregulated by Liraglutide. The reduction of BW and improvement of insulin resistance with Liraglutide may be partially explained by AC3 activation.
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: S
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Guangxi Medical University, Nanning, China.|Department of Oncology-Pathology, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Lu
authors.affiliation: Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: H F
authors.initials: HF
authors.lastname: Gu
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: N
authors.initials: N
authors.lastname: Xia
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D000069450:Liraglutide / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000517:prevention & control*; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide; D000262:Adenylyl Cyclases; C421784:adenylate cyclase 3