Sleeve Gastrectomy Reduces Blood Pressure in Obese (fa/fa) Zucker Rats

Rodríguez, Amaia; Becerril, Sara; Valentí, Víctor; Ramírez, Beatriz; Martín, Marina; Méndez‐Giménez, Leire; Lancha, Andoni; Calderón, Pablo del Sol; Catalán, Victoria; Burrell, Marı́a A.; Gómez-Ambrosi, Javier; Frühbeck, Gema

doi:10.1007/s11695-011-0562-3

Cited by 15 publications

(6 citation statements)

References 30 publications

(39 reference statements)

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“…Therefore, we were able to assess the body mass-independent effect of VSG surgery on AP. Similar to previous studies in rats ( Rodríguez et al, 2012a , b ), heart mass did not significantly differ between groups ( Fig. 1 D).…”

Section: Resultssupporting

confidence: 90%

“…Similar to previous studies, we show that VSG surgery decreases circulating leptin concentrations in comparison to sham-operated ad libitum -fed mice, but not weight-matched controls, suggesting that leptin does not contribute to the body mass-independent decreases in AP after VSG ( Cummings et al, 2012 ). In line with this, previous work in a leptin receptor-deficient rat model reports reductions in AP after VSG despite the lack of a functional leptin receptor ( Rodríguez et al, 2012b ). Post-operative decreases in circulating ghrelin concentrations have been suggested to contribute to metabolic improvements after VSG surgery.…”

Section: Discussionsupporting

confidence: 78%

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Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice

McGavigan

Henseler

Garibay

et al. 2017

Disease Models &Amp; Mechanisms

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Bariatric surgery, such as vertical sleeve gastrectomy (VSG), causes remarkable improvements in cardiometabolic health, including hypertension remission. However, the mechanisms responsible remain undefined and poorly studied. Therefore, we developed and validated the first murine model of VSG that recapitulates the blood pressure-lowering effect of VSG using gold-standard radiotelemetry technology. We used this model to investigate several potential mechanisms, including body mass, brain endoplasmic reticulum (ER) stress signaling and brain inflammatory signaling, which are all critical contributors to the pathogenesis of obesity-associated hypertension. Mice fed on a high-fat diet underwent sham or VSG surgery and radiotelemeter implantation. Sham mice were fed ad libitum or were food restricted to match their body mass to VSG-operated mice to determine the role of body mass in the ability of VSG to lower blood pressure. Blood pressure was then measured in freely moving unstressed mice by radiotelemetry. VSG decreased energy intake, body mass and fat mass. Mean arterial blood pressure (MAP) was reduced in VSG-operated mice compared with both sham-operated groups. VSG-induced reductions in MAP were accompanied by a body mass-independent decrease in hypothalamic ER stress, hypothalamic inflammation and sympathetic nervous system tone. Assessment of gut microbial populations revealed VSG-induced increases in the relative abundance of Gammaproteobacteria and Enterococcus, and decreases in Adlercreutzia. These results suggest that VSG reduces blood pressure, but this is only partly due to the reduction in body weight. VSG-induced reductions in blood pressure may be driven by a decrease in hypothalamic ER stress and inflammatory signaling, and shifts in gut microbial populations.

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Section: Resultssupporting

confidence: 90%

Section: Discussionsupporting

confidence: 78%

Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice

McGavigan

Henseler

Garibay

et al. 2017

Disease Models &Amp; Mechanisms

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“…Although HP diets have been shown to counteract the increase in blood pressure in overweight human subjects (Papakonstantinou et al 2010), neither obesity nor protein level affected blood pressure in the present study. The lack of increased blood pressure in obese fa/fa Zucker rats compared to their lean counterparts has been reported previously (Rodriguez et al 2012).…”

Section: Discussionsupporting

confidence: 61%

Mixed compared with single-source proteins in high-protein diets affect kidney structure and function differentially in obesefa/faZucker rats

Devassy

Wojcik

Ibrahim

et al. 2017

Appl. Physiol. Nutr. Metab.

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Questions remain regarding the potential negative effects of dietary high protein (HP) on kidney health, particularly in the context of obesity in which the risk for renal disease is already increased. To examine whether some of the variability in HP effects on kidney health may be due to source of protein, obese fa/fa Zucker rats were given HP (35% of energy from protein) diets containing either casein, soy protein, or a mixed source of animal and plant proteins for 12 weeks. Control lean and obese rats were given diets containing casein at normal protein (15% of energy from protein) levels. Body weight and blood pressure were measured, and markers of renal structural changes, damage, and function were assessed. Obesity alone resulted in mild renal changes, as evidenced by higher kidney weights, proteinuria, and glomerular volumes. In obese rats, increasing the protein level using the single, but not mixed, protein sources resulted in higher renal fibrosis compared with the lean rats. The mixed-protein HP group also had lower levels of serum monocyte chemoattractant protein-1, even though this diet further increased kidney and glomerular size. Soy and mixed-protein HP diets also resulted in a small number of damaged glomeruli, while soy compared with mixed-protein HP diet delayed the increase in blood pressure over time. Since obesity itself confers added risk of renal disease, an HP diet from mixed-protein sources that enables weight loss but has fewer risks to renal health may be advantageous.

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“…Obesity is associated with hyperleptinemia, an imbalance of ghrelin isoforms as well as with an impairment of transduction signal in effector organs, suggesting the pivotal role of leptin and ghrelin in the control of adiposity and cardiovascular homeostasis. Sleeve gastrectomy, an effective bariatric procedure for the treatment of morbid obesity, is associated with a reduction of blood pressure, but not heart rate, in genetically obese Zucker fa/fa rats beyond weight loss [ 106 ]. The same was true in an animal model of diet-induced obesity that showed a further reduction of heart rate values without loss of cardiac mass [ 107 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Molecular Aspects of Ghrelin and Leptin in the Control of Adipobiology and the Cardiovascular System

Rodríguez

2014

Obes Facts

Self Cite

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Ghrelin and leptin show opposite effects on energy balance. Ghrelin constitutes a gut hormone that is secreted to the bloodstream in two major forms, acylated and desacyl ghrelin. The isoforms of ghrelin not only promote adiposity by the activation of hypothalamic orexigenic neurons but also directly stimulate the expression of several fat storage-related proteins in adipocytes, including ACC, FAS, LPL and perilipin, thereby stimulating intracytoplasmic lipid accumulation. Moreover, both acylated and desacyl ghrelin reduce TNF-α-induced apoptosis and autophagy in adipocytes, suggesting an anti-inflammatory role of ghrelin in human adipose tissue. On the other hand, leptin is an adipokine with lipolytic effects. In this sense, leptin modulates via PI3K/Akt/mTOR the expression of aquaglyceroporins such as AQP3 and AQP7 that facilitate glycerol efflux from adipocytes in response to the lipolytic stimuli via its translocation from the cytosolic fraction (AQP3) or lipid droplets (AQP7) to the plasma membrane. Ghrelin and leptin also participate in the homeostasis of the cardiovascular system. Ghrelin operates as a cardioprotective factor with increased circulating acylated ghrelin concentrations in patients with left ventricular hypertrophy (LVH) causally related to LV remodeling during the progression to LVH. Additionally, leptin induces vasodilation by inducible NO synthase expression (iNOS) in the vascular wall. In this sense, leptin inhibits the angiotensin II-induced Ca²⁺ increase, contraction and proliferation of VSMC through NO-dependent mechanisms. Together, dysregulation of circulating ghrelin isoforms and leptin resistance associated to obesity, type 2 diabetes, or the metabolic syndrome contribute to cardiometabolic derangements observed in these pathologies.

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Sleeve Gastrectomy Reduces Blood Pressure in Obese (fa/fa) Zucker Rats

Abstract: Our findings provide evidence of the beneficial effects of sleeve gastrectomy on blood pressure values in addition to the weight loss in obese (fa/fa) Zucker rats independently of surgical trauma and food intake reduction.

Cited by 15 publications

References 30 publications

Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice

Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice

Mixed compared with single-source proteins in high-protein diets affect kidney structure and function differentially in obesefa/faZucker rats

Novel Molecular Aspects of Ghrelin and Leptin in the Control of Adipobiology and the Cardiovascular System

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