title: Saturated high-fat diet-induced obesity increases adenylate cyclase of myocardial β-adrenergic system and does not compromise cardiac function.
abstract: Obesity is a worldwide pandemic associated with high incidence of cardiovascular disease. The mechanisms by which the obesity leads cardiac dysfunction are not fully elucidated and few studies have evaluated the relationship between obesity and proteins involved in myocardial β-adrenergic (βA) system. The purpose of this study was to evaluate the cardiac function and βA pathway components in myocardium of obese rats. Male Wistar rats were distributed into two groups: control (n = 17; standard diet) and obese (n = 17; saturated high-fat diet) fed for 33 weeks. Nutritional profile and comorbidities were assessed. Cardiac structure and function was evaluated by macroscopic postmortem, echocardiographic and isolated papillary muscle analyzes. Myocardial protein expression of β1- and β2-adrenergic receptors, Gαs protein, adenylate cyclase (AC) and protein kinase A (PKA) was performed by Western blot. Cardiac cyclic adenosine monophosphate (cAMP) levels and PKA activity were assessed by ELISA Obese rats showed increased adiposity index (P < 0.001) and several comorbidities as hypertension, glucose intolerance, insulin resistance, and dyslipidemia compared with control rats. Echocardiographic assessment revealed increased left atrium diameter (C: 4.98 ± 0.38 vs. Ob: 5.47 ± 0.53, P = 0.024) and posterior wall shortening velocity (C: 37.1 ± 3.6 vs. Ob: 41.8 ± 3.8, P = 0.007) in obese group. Papillary muscle evaluation indicated that baseline data and myocardial responsiveness to isoproterenol stimulation were similar between the groups. Protein expression of myocardial AC was higher in obese group than in the control (C: 1.00 ± 0.21 vs. Ob: 1.25 ± 0.10, P = 0.025), whereas the other components were unchanged. These results suggest that saturated high-fat diet-induced obesity was not effective in triggering cardiac dysfunction and impair the beta-adrenergic signaling.
authors: Department of Internal Medicine, Medical School São Paulo State University "Júlio de Mesquita Filho", Botucatu, São Paulo, Brazil dani.vileigas@gmail.com.
authors: Danielle F
authors: DF
authors: Vileigas
authors: Department of Internal Medicine, Medical School São Paulo State University "Júlio de Mesquita Filho", Botucatu, São Paulo, Brazil.
authors: Adriana F
authors: AF
authors: de Deus
authors: Department of Internal Medicine, Medical School São Paulo State University "Júlio de Mesquita Filho", Botucatu, São Paulo, Brazil.
authors: Danielle C T
authors: DC
authors: da Silva
authors: Department of Internal Medicine, Medical School São Paulo State University "Júlio de Mesquita Filho", Botucatu, São Paulo, Brazil.
authors: Loreta C
authors: LC
authors: de Tomasi
authors: Department of Internal Medicine, Medical School São Paulo State University "Júlio de Mesquita Filho", Botucatu, São Paulo, Brazil.
authors: Dijon H S
authors: DH
authors: de Campos
authors: Department of Internal Medicine, Medical School São Paulo State University "Júlio de Mesquita Filho", Botucatu, São Paulo, Brazil.
authors: Caroline S
authors: CS
authors: Adorni
authors: Department of Internal Medicine, Medical School São Paulo State University "Júlio de Mesquita Filho", Botucatu, São Paulo, Brazil.
authors: Scarlet M
authors: SM
authors: de Oliveira
authors: Department of Internal Medicine, Medical School São Paulo State University "Júlio de Mesquita Filho", Botucatu, São Paulo, Brazil.
authors: Paula G
authors: PG
authors: Sant'Ana
authors: Department of Internal Medicine, Medical School São Paulo State University "Júlio de Mesquita Filho", Botucatu, São Paulo, Brazil.
authors: Katashi
authors: K
authors: Okoshi
authors: Department of Biostatistics, Biosciences Institute São Paulo State University "Júlio de Mesquita Filho", Botucatu, São Paulo, Brazil.
authors: Carlos R
authors: CR
authors: Padovani
authors: Department of Internal Medicine, Medical School São Paulo State University "Júlio de Mesquita Filho", Botucatu, São Paulo, Brazil.
authors: Antonio C
authors: AC
authors: Cicogna
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000378:metabolism*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism; D001344:Autopsy; D059305:Diet, High-Fat / Q000009:adverse effects* / Q000379:methods; D006321:Heart / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D010210:Papillary Muscles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013566:Sympathomimetics / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D013566:Sympathomimetics; D000262:Adenylyl Cyclases; D007545:Isoproterenol
keywords: Cardiac remodeling; obesity; saturated high‐fat diet; β‐adrenergic pathway