title: Renin-angiotensin system blockers regulate the metabolism of isolated fat cells in vitro.
abstract: Due to the presence of the renin-angiotensin system (RAS) in tissues and its specific influence on white adipose tissue, fat cells are possible targets of pharmacological RAS blockers commonly used as anti-hypertensive drugs. In the present study, we investigated the effects of different RAS blockers on fat cell metabolism, more specifically on lipolysis, lipogenesis and oxidation of energy substrates. Isolated primary adipocytes were incubated with different RAS blockers (aliskiren, captopril and losartan) in vitro for 24 h and lipolysis, lipogenesis and glucose oxidation capacities were determined in dose-response assays to a β-adrenergic agonist and to insulin. Although no change was found in lipolytic capacity, the RAS blockers modulated lipogenesis and glucose oxidation in a different way. While captopril decreased insulin-stimulated lipogenesis (-19% of maximal response and -60% of insulin responsiveness) due to reduced glucose derived glycerol synthesis (-19% of maximal response and 64% of insulin responsiveness), aliskiren increased insulin-stimulated glucose oxidation (+49% of maximal response and +292% of insulin responsiveness) in fat cells. Our experiments demonstrate that RAS blockers can differentially induce metabolic alterations in adipocyte metabolism, characterized by a reduction in lipogenic responsiveness or an increase in glucose oxidation. The impact of RAS blockers on adipocyte metabolism may have beneficial implications on metabolic disorders during their therapeutic use in hypertensive patients.
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: R de O
authors.initials: Rde O
authors.lastname: Caminhotto
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: R A L
authors.initials: RA
authors.lastname: Sertié
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: S
authors.initials: S
authors.lastname: Andreotti
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: A B
authors.initials: AB
authors.lastname: Campaãa
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: F B
authors.initials: FB
authors.lastname: Lima
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D005650:Fumarates / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects; D008066:Lipolysis / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology; D008297:Male; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; C446481:aliskiren; D002216:Captopril; D005947:Glucose; D019808:Losartan; D005990:Glycerol