The major finding from the present study was that the natural rise in plasma leptin with weight-gain is insufficient to counterbalance high blood pressure associated with obesity, additional increases of circulating leptin levels with adenoviral leptin gene therapy led to normalisation of blood pressure in high-fat diet-induced obese and hypertensive rats.
The study confirmed that shorter alleles of microsatellites in the 3' flanking region of leptin are significantly associated with hypertension, however, the underlying mechanism remains unknown.
Furthermore, the Gln223Arg polymorphism was significantly associated with plasma leptin levels (p<0.001), while no correlations between Lys109Arg SNP and hypertension were found.
Many experimental and clinical studies have demonstrated that elevated leptin concentration in patients with obesity/metabolic syndrome contributes to the pathogenesis of cardiovascular disorders including arterial hypertension, atherosclerosis, restenosis after coronary angioplasty and myocardial hypertrophy.
Our results suggest that the Gln223Arg polymorphism of the leptin receptor is significantly associated with plasma leptin levels and left ventricular hypertrophy in hypertension.
In this meta-analysis, we summarized the association of the II/I polymorphism in leptin gene and Gln223Arg polymorphism in LEPR gene with hypertension and circulating leptin.
Specific mutations in the leptin and the melaninocortin receptor genes in animal models of obesity without hypertension, the actions of α-melanocyte stimulating hormone, and SNS activity in obesity-related hypertension may promote recognition of protective and promoting factors for hypertension in obesity.
Hence, central leptin employs TNFα to mediate the diurnal blood pressure elevation in physiology while enhancement of this mechanism can contribute to hypertension development.
In this model, neonatal leptin supplementation restores the physiologic leptin surge, attenuates the leptin-triggered sympathetic activation in adulthood and prevents leptin- or stress-evoked hypertension.
Finally, it might be postulated that alterations of mitochondrial dynamics in white adipose tissue could contribute to the development and maintenance of hypertension in obesity situations through leptin overproduction.
Hence, neural control of blood pressure is mediated by a signaling network between leptin, TNFα, melanocortin, and glutamate and changes in dynamics due to central excess leptin and TNFα mediate the switch from normal physiology to obesity-related hypertension.
There is now convincing evidence from animal studies that major signals such as leptin and insulin have a sympathoexcitatory action in the hypothalamus to cause hypertension.
VPA administration prevented the progression of hypertension and inhibited the increase in expression of HDAC1 and RAS components.VPA did not affect plasma leptin level.
In this study, we identified the variables that predict BP response to CPAP.24-h ambulatory BP monitoring (ABPM), C-reactive protein (CRP), leptin, adiponectin and 24-h urinary catecholamine were measured before and after 6 months of CPAP in obstructive sleep apnoea (OSA) patients.Overall, 88 middle-aged, obese male patients with severe OSA (median apnoea-hypopnoea index 42 events·h<sup>-1</sup>) were included; 28.4% had hypertension.
The MHO individuals with abnormal adipokines were significantly more likely to developing hypertension (high leptin, relative risk 11.04; 95% confidence interval, 1.18-103.35; and high leptin/adiponectin ratio, relative risk 9.88; 95% confidence interval, 1.11-87.97) compared to metabolically healthy normal-weight individuals with normal adipokine levels.
Leptin appears as a new direct regulator of adrenal aldosterone production and leptin-mediated aldosterone production is a novel candidate mechanism underlying obesity-associated hypertension, particularly in females.