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.

Renin inhibition improves metabolic syndrome, and reduces angiotensin II levels and oxidative stress in visceral fat tissues in fructose-fed rats

“…For example, Kalupahana et al demonstrated that the major sources of oxidative stress in adipose tissues are the activation of membrane-associated NADPH-oxidases by Ang II stimulation in transgenic mice overexpressing angiotensinogen in adipose tissues, and they demonstrated that RAS overactivation causes systemic insulin resistance [ 14 ]. In the in vitro study of Caminhotto et al, lipolysis, lipogenesis and glucose oxidation capacities of different RAS blockers (aliskiren, captopril, and losartan) were investigated through co-incubated isolated primary adipocytes and different RAS blockers in vitro for 24 h [ 48 ]. Concerning the effect of aliskiren treatment, aliskiren treatment only increased glucose oxidation capacities following insulin stimulation in fat cells, which implies that in vitro aliskiren treatment has an improvement of oxidative stress in isolated primary adipocytes.…”

“…Concerning the effect of aliskiren treatment, aliskiren treatment only increased glucose oxidation capacities following insulin stimulation in fat cells, which implies that in vitro aliskiren treatment has an improvement of oxidative stress in isolated primary adipocytes. Also, Caminhotto et al suggested that the in vivo effects of aliskiren treatment on adipose oxidative stress merit to be further clarified [ 48 ]. In our in vivo study, the data showed that aliskiren treatment reduced visceral adipose Ang II and NOX isoforms expressions, increased adipose SOD activity, and diminished adipose lipid peroxide in fructose-fed rats, which indicated that in vivo aliskiren treatment had the improvement of oxidative stress in visceral adipocytes.…”

Inhibition of AT1 receptors by losartan affects myocardial slow force response in healthy but not in monocrotaline-treated young rats

“…Therefore, the lack of the effect of losartan on slow force changes in the myocardium of monocrotaline-treated rats may reflect either the silencing of angiotensin secretion or augmented activation of AT 1 receptors under pathological remodeling of cardiac cell in this model of right ventricular failure. A direct effect of losartan on metabolic processes like glucose oxidation, as recently reported in fat cells (Caminhotto et al 2016), is hardly believed in the muscles because of the great suppression of SFR in normal myocardium under perfusion by losartan and the absence of this effect in "failing" muscles. Authors note that our ambient conditions were out of physiological.…”