title: Pivotal role of cAMP in the activation of liver glycogen breakdown in high-fat diet fed mice.
abstract: OBJECTIVE
  Liver glycogen catabolism was evaluated in male Swiss mice fed a high-fat diet rich in saturated fatty acids (HFD) or normal fat diet (NFD) during one week.
  
  
  METHODS
  Liver glycogenolysis (LG) and liver glucose production (LGP) were measured either under basal or stimulated conditions (infusion of glycogenolytic agents). Thus, isolated perfused livers from HFD and NFD mice were infused with glycogenolytic agents, i.e., glucagon, epinephrine, phenylephrine, isoproterenol, adenosine-3'-5'-cyclic monophosphate (cAMP), N(6),2'-O-dibutyryl-cAMP (DB-cAMP), 8-bromoadenosine-cAMP (8-Br-cAMP) or N(6)-monobutyryl-cAMP (N6-MB-cAMP). Moreover, glycemia and liver glycogen content were measured.
  
  
  RESULTS
  Glycemia, liver glycogen content and basal rate of LGP and LG were not influenced by the HFD. However, LGP and LG were lower (p<0.05) in HFD mice during the infusions of glucagon (1 nM), epinephrine (20 μM) or phenylephrine (20 μM). In contrast, the activation of LGP and LG during the infusion of isoproterenol (20 μM) was not different (HFD vs. NFD). Because glucagon showed the most prominent response, the effect of cAMP, its intracellular mediator, on LGP and LG was investigated. cAMP (150 μM) showed lower activation of LGP and LG in the HFD group. However, the activation of LGP and LG was not influenced by HFD whether DB-cAMP (3 μM), 8-Br-cAMP (3 μM) or N6-MB-cAMP (3 μM) were used.
  
  
  CONCLUSIONS
  The activation of LGP and LG depends on the intracellular availability of cAMP. It can be concluded that cAMP played a pivotal role on the activation of LG in high-fat diet fed mice.
authors: Department of Pharmacology and Therapeutic, State University of Maringá, Maringá, PR 87020-900, Brazil.
authors: Fabiana P M
authors: FP
authors: Schiavon
authors: Department of Pharmacology and Therapeutic, State University of Maringá, Maringá, PR 87020-900, Brazil.
authors: Any de Castro Ruiz
authors: Ade C
authors: Marques
authors: Ingá Faculty, Maringá, PR 87035-510, Brazil.
authors: Marcia A
authors: MA
authors: Carrara
authors: Department of Physiological Sciences, State University of Londrina, Londrina, PR 86051-990, Brazil.
authors: Helenir Medri
authors: HM
authors: de Souza
authors: Department of Pharmacology and Therapeutic, State University of Maringá, Maringá, PR 87020-900, Brazil.
authors: Christiano Rodrigues
authors: CR
authors: Schamber
authors: Department of Physiology and Biophysics, University of São Paulo, São Paulo, SP 05508-900, Brazil.
authors: Rui
authors: R
authors: Curi
authors: Department of Pharmacology and Therapeutic, State University of Maringá, Maringá, PR 87020-900, Brazil. Electronic address: rbbazotte@uem.br.
authors: Roberto B
authors: RB
authors: Bazotte
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D059305:Diet, High-Fat; D050261:Glycogenolysis; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D051379:Mice
chemical_list: D008112:Liver Glycogen; D000242:Cyclic AMP
keywords: Cyclic AMP; Glycogenolysis; High-fat diet; Liver; Mice