Non-esterified fatty acids and blood pressure elevation: a mechanism for hypertension in subjects with obesity/insulin resistance?

Abstract

The prevalence of hypertension in individuals with obesity or type II diabetes is substantially elevated. Increased levels of non-esterified fatty acids (NEFAs) in abdominally obese subjects were reported to contribute in the development of various disturbances related to the metabolic syndrome, such as hepatic and peripheral insulin resistance (IR), dyslipidaemia, b-cell apoptosis, endothelial dysfunction and others. However, the involvement of NEFAs in the development of hypertension has been much less studied in comparison to other mechanisms linking IR and central obesity with blood pressure (BP) elevation. This article reviews the existing evidence on the relation between NEFA and hypertension in an attempt to shed a light on it. In vivo data from both animal and human studies support that acute plasma NEFA elevation leads to increase in BP levels, whereas epidemiological evidence suggests a link between increased NEFA levels and hypertension. Further, accumulating data indicate the existence of several pathways through which NEFAs could promote BP elevation, that is a 1 -adrenergic stimulation, endothelial dysfunction, increase in oxidant stress, stimulation of vascular cell's growth and others. The above data support a possible important role of NEFA in hypertension development in patients with obesity and the metabolic syndrome and raise hypotheses for future research.

Implicações da lipoclasia dermossônica no metabolismo energético e na composição corporal de ratos Wistar saudáveis

“…They also report that the increased FFA flow originating from adipose tissues to non-adipose ones, in general worsens the signaling of the insulin receptor substrate 1 (IRS-1) [21][22][23][24][25][26][27] , suggesting that the IR observed in the animals treated with DLC might have occurred due to the lipotoxic effects of the FFA in the IRS-1 signaling, bringing about dysfunctions in the activation cascade of this receptor [18][19][20][21] , which was indicated by the high values of HOMA-IR. Other studies show that the inhibition and/or loss of sensibility of the IRS-1 may facilitate the accumulation of tissue fat through the reduction of the lipolytic activity of the insulin, leading to the resterification of the FFA in the muscles and other tissues, a critical effect which is currently being discussed as lipotoxicity [17][18][19][20][21][22][23][24] .…”

“…Studies carried out by Lewis et al 18 and other authors [18][19][20][21][22][23] describe that the maintenance of high levels of circulating, non-esterified FFA give rise to deleterious effects in the energetic biochemistry and in the cellular metabolism. They also report that the increased FFA flow originating from adipose tissues to non-adipose ones, in general worsens the signaling of the insulin receptor substrate 1 (IRS-1) [21][22][23][24][25][26][27] , suggesting that the IR observed in the animals treated with DLC might have occurred due to the lipotoxic effects of the FFA in the IRS-1 signaling, bringing about dysfunctions in the activation cascade of this receptor [18][19][20][21] , which was indicated by the high values of HOMA-IR.…”

“…Moreover, a low level of highfrequency ultrasound irradiation was used, which prevented the spreading effect of the mechanic wave, a fact that may imply a remarkable sonochemical effect of the LIUST on the WAT (Figures 2A and B). Considering the lipolytic effects of the DLC on the subcutaneous WAT [6][7][8] , the RET and PR fat pad reductions are believed to be related with the endocrine, paracrine, and autocrine actions of the adipokines liberated by the subcutaneous WAT 17,[18][19][20][21]24,28 during the DLC; or they could have occurred because of an increase in the local enzymatic activity (LPL-lipoprotein and LHS-hormone-sensitive lipases) stimulated by the noradrenalin released in the sympathetic nerve endings of the subcutaneous WAT 6,7,9,30 after the DLC. Such effects, which corroborate the high levels of LPL obtained in this study ( Table 2) are indicative of noteworthy sonochemical actions of the 3MHz US in the subcutaneous inguinal and abdominal WAT 17,18,24 .…”

“…These and other effects of low-intensity ultrasound therapy (LIUST) on the lipid and glycemic metabolism fostered several new possibilities for therapy applications in the treatment of obesity and type-II diabetes mellitus (DM 2 ). However, recents studies on thermogenesis, obesity, and physical activity revealed that the increase in plasma FFA is involved with the conditions of insulin preresistance (IR), obesity, and DM 2, and have several implications in the pathogenesis of metabolic syndrome (MS) [17][18][19][20][21][22][23][24] .…”

Peroxisome proliferator-activated receptor-α activator fenofibrate prevents high-fat diet-induced renal lipotoxicity in spontaneously hypertensive rats

“…1,2 It has been suggested that the development and progression of hypertension in an obese patient induces the activation of the systemic renin-angiotensin system (RAS) and the sympathetic nervous system. 3,4 In addition, it increases asymmetric dimethylarginine concentrations and vascular tone created by the reduced bioavailability of nitric oxide (NO) owing to increased oxidative stress. 5,6 Recent reports have demonstrated that it is not the systemic but the local (tissue specific) RAS activation that causes hypertension and renal damage [7][8][9] associated with local oxidative stress.…”