Selective leptin resistance revisited

Mark, Allyn L.

doi:10.1152/ajpregu.00180.2013

Cited by 142 publications

(136 citation statements)

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“…Leptin sensitivity for cardiovascular actions during aging, however, is unknown. It is possible to observe divergent effects in this regard as previous studies have shown that resistance is selective to the metabolic, but not cardiovascular, actions of leptin in obese animal models perhaps due to brain-and signaling pathway-specific mechanisms (28). Interestingly, the leptin injection did produce a transient decrease in blood pressure in older rats suggesting at least some responsiveness in cardiovascular pathways in the dorsal medulla during aging.…”

Section: Discussionmentioning

confidence: 97%

Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats

Arnold

Diz

2014

American Journal of Physiology-Heart and Circulatory Physiology

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Arnold AC, Diz DI. Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats. Am J Physiol Heart Circ Physiol 307: H1539 -H1546, 2014. First published September 26, 2014; doi:10.1152/ajpheart.00282.2014.-The decline in cardiovagal baroreflex function that occurs with aging is accompanied by an increase in circulating leptin levels. Our previous studies showed that exogenous leptin impairs the baroreflex sensitivity for control of heart rate in younger rats, but the contribution of this hormone to baroreflex dysfunction during aging is unknown. Thus we assessed the effect of bilateral leptin microinjection (500 fmol/60 nl) within the solitary tract nucleus (NTS) on the baroreflex sensitivity in older (66 Ϯ 2 wk of age) urethane/chloralose anesthetized SpragueDawley rats with elevated circulating leptin levels. In contrast to the 63% reduction observed in younger rats, leptin did not alter the baroreflex sensitivity for bradycardia evoked by phenylephrine in older rats (0.76 Ϯ 0.19 baseline vs. 0.71 Ϯ 0.15 ms/mmHg after leptin; P ϭ 0.806). We hypothesized that this loss of sensitivity reflected endogenous suppression of the baroreflex by elevated leptin, rather than cardiovascular resistance to the peptide. Indeed, NTS administration of a leptin receptor antagonist (75 pmol/120 nl) improved the baroreflex sensitivity for bradycardia in older rats (0.73 Ϯ 0.13 baseline vs. 1.19 Ϯ 0.26 at 10 min vs. 1.87 Ϯ 0.32 at 60 min vs. 1.22 Ϯ 0.54 ms/mmHg at 120 min; P ϭ 0.002), with no effect in younger rats. There was no effect of the leptin antagonist on the baroreflex sensitivity for tachycardia, responses to cardiac vagal chemosensitive fiber activation, or resting hemodynamics in older rats. These findings suggest that the actions of endogenous leptin within the NTS, either produced locally or derived from the circulation, contribute to baroreflex suppression during aging. autonomic; aging; arterial baroreflex; leptin THE ARTERIAL BARORECEPTOR reflex is critically involved in short-term regulation of blood pressure through modulation of central autonomic pathways that control sympathetic and parasympathetic outflow to peripheral cardiovascular organs. During aging, there is impairment of the baroreflex sensitivity (BRS) for control of heart rate (HR) (13, 15, 32), a marker of parasympathetic tone mediated at the level of the solitary tract nucleus (NTS) in the dorsal medulla (2), due to changes in central neuronal and peripheral vascular function. Importantly, baroreflex dysfunction is permissive to chronic sympathetic activation to increase blood pressure and its variability and is an independent risk factor for cardiovascular morbidity and mortality (25,42). The precise mechanisms involved in agerelated baroreflex impairments, however, are not fully understood. The identification of hormones or other factors that modulate autonomic brainstem regions, such as the NTS, may therefore improve our understanding of the decline in baroreflex function that occurs with aging.Aging is...

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Section: Discussionmentioning

confidence: 97%

Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats

Arnold

Diz

2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…18,19 In the case of leptin, however, prevailing evidence suggests that the opposite is also true, namely that leptin may trigger central and peripheral sympathoexcitation. 38,39 This possibility has been recently strengthened by the results of a microneurographic study showing that in healthy normoweight subjects acute infusion of leptin triggers a significant increase in MSNA. 40 It is thus conceivable to conclude that the sympathoinhibitory effects of sleeve gastrectomy are mediated, at least in part, by the reduction in the elevated levels of plasma leptin, which activate the sympathetic nervous system.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Sympathoinhibitory Effects of Surgically Induced Weight Loss in Severe Obese Patients

Seravalle

Colombo

et al. 2014

Hypertension

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L ong-term prospective studies have recently shown that bariatric surgery significantly reduces the risk of death in severely obese patients.1 This has been confirmed by retrospective analyses of a large cohort of obese individuals in whom surgery-related reductions in body weight were associated with a significant reduction in death rate compared with obese individuals followed under dietary and medical treatment. [2][3][4] It is a widespread belief that the protective effect of bariatric surgery in obese patients may perhaps be related to a reduction of body weight per se but that the concomitant improvement of the array of risk factors commonly associated with obesity, for example, alterations in lipid and glucose metabolism, is likely to play a major role. [5][6][7] In this context, however, little attention has to date been given to whether bariatric surgery is also associated with the improvement of another adverse phenomenon of obesity (ie, sympathetic activation). 8,9 The only information available comes from 3 studies that assessed sympathetic tone by making use of spectral analysis of heart rate signal or 24-hour norepinephrine urinary excretion [10][11][12] (ie, approaches that display major intrinsic limitations not allowing to provide any direct insight on the effects of the intervention on central sympathetic outflow, as the microneurographic technique only allows to achieve 13 .) The issue has pathophysiological and clinical relevance because sympathetic activation has been shown to be an adverse prognostic factor in several clinical conditions.14-17 Furthermore, evidence has been obtained that sympathetic overdrive may cause or worsen insulin resistance, 18,19 thus contributing to a common metabolic alteration in obesity.Abstract-Weight loss improves insulin sensitivity and exerts sympathomodulatory effects. No data, however, are available on the effects of the weight loss induced by vertical sleeve gastrectomy on sympathetic neural drive, insulin sensitivity, and their reciprocal cross talks. In 10 severe obese hypertensives (age, 54.0±2.3 years [mean±SEM]), we measured sphygmomanometric blood pressure, heart rate, body mass index, homeostatic model assessment index, plasma leptin, muscle sympathetic nerve traffic (microneurography), and baroreflex sensitivity (vasoactive drug technique). Measurements were performed 2 to 3 days before surgery and repeated 6 and 12 months after the procedure. Ten matched hypertensive obeses not undergoing gastrectomy served as controls. Six months after bariatric surgery, a significant (P<0.05) reduction in body mass index (−9.1±1.4 kg/m 2 ), sphygmomanometric systolic blood pressure (−10.2±4.5 mm Hg), heart rate (−11.0±2.4 bpm), homeostatic model assessment index (−3-3±1.3 AU), plasma leptin (−53.6±8.8 μg/L), and muscle sympathetic nerve traffic (−15.0±3.4 bursts/100 heart beats) was observed. The weight loss, the plasma leptin reduction, and the sympathetic inhibition were maintained after 12 months, whereas homeostatic model assessment index showed a tendency ...

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“…More recently, it has been suggested that this resistance is selective, whereby the cardiovascular effects of leptin remain intact, while the metabolic effects of leptin are abolished (26). Current research on the mechanisms underlying selective leptin resistance (SLR) focuses on deficits in leptin signaling.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin AT1A receptors on leptin receptor–expressing cells control resting metabolism

Claflin¹,

Sandgren²,

Lambertz³

et al. 2017

Journal of Clinical Investigation

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Selective leptin resistance revisited

Cited by 142 publications

References 167 publications

Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats

Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats

Long-Term Sympathoinhibitory Effects of Surgically Induced Weight Loss in Severe Obese Patients

Angiotensin AT1A receptors on leptin receptor–expressing cells control resting metabolism

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