Abstract P211: Intra-abdominal Lipectomy Normalizes Arterial Stiffness and Blood Pressure via Reduction in 20-HETE

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Amanda A Soler ◽  
Brenda Hutcheson ◽  
Jenny Yang ◽  
Chastity Bradford ◽  
Frank F Zhang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Large Artery ◽  
The Metabolic Syndrome ◽  
Elastin Degradation ◽  
Artery Stiffness ◽  
Abdominal Lipectomy ◽  
Visceral Adipose

Increased intra-abdominal (visceral) adipose tissue is a key feature of the metabolic syndrome affecting over 30% of the U.S. population. Expansion of visceral adipose tissue is linked to the development of hypertension and is a risk factor for cardiovascular disease that can ultimately lead to end-organ damage. While reduction in visceral adipose tissue volume offers cardioprotective effects, the cardiovascular mechanisms behind these beneficial effects remain unclear. In this study, we removed ~90% of visceral adipose tissue (=~5% body weight) by intra-abdominal lipectomy and assessed large arterial stiffness, large artery structural matrix components, and blood pressure in a metabolic syndrome rat model (JCR:LA-cp, JCR). Large artery stiffness was significantly elevated in JCR vs. normal (Sprague Dawley, SD) rats (75±2% JCR vs. SD (carotid)) with a concomitant significant increase in MMP12-dependent elastin degradation (3-6 fold vs. SD). Intra-abdominal lipectomy normalized large artery stiffness, blocked MMP12 activation and reduced elastin degradation in JCR animals (~75% (carotid) vs. untreated JCR). Likewise, hypertension in JCR animals was significantly attenuated by intra-abdominal lipectomy (MABP=156±3 mmHg JCR vs. 90±6 mmHg SD vs. 132±4 mmHg JCR+lipectomy). 20-hydroxyeicosatetraeonic acid (20-HETE), an arachidonic acid metabolite known to be a potent vasoconstrictor in resistance arteries, was significantly elevated in the visceral adipose tissue of JCR rats (~6 fold vs. SD). Intra-abdominal lipectomy normalized 20-HETE levels in JCR rats. Like intra-abdominal lipectomy, 20-HETE antagonists restored large artery elasticity, blocked MMP12 activation and elastin degradation, and significantly decreased blood pressure (125±3 mmHg JCR+20-HETE antagonists) in JCR rats. Thus, 20-HETE may be an important adipokine that mediates the adverse effects of expanded visceral fat volume in the metabolic syndrome and its inhibition may provide a pharmacological approach for the management of central obesity-driven large artery stiffness and hypertension.

Enhanced fatty acid uptake in visceral adipose tissue is not reversed by weight loss in obese individuals with the metabolic syndrome

Diabetologia ◽  
2014 ◽  
Vol 58 (1) ◽  
pp. 158-164 ◽  
Author(s):  
Marco Bucci ◽  
Anna C. Karmi ◽  
Patricia Iozzo ◽  
Barbara A. Fielding ◽  
Antti Viljanen ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Visceral Adipose Tissue ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
The Metabolic Syndrome ◽  
Visceral Adipose

Abstract 040: Comparison of Effects of Reux en Y Gastric Bypass and Intra-abdominal Lipectomy on Cardiovascular Function in the Metabolic Syndrome

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Amanda Soler ◽  
Brenda Hutcheson ◽  
Jenny Yang ◽  
Chastity Bradford ◽  
Frank Zhang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Gastric Bypass ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Carotid Artery ◽  
Abdominal Adipose Tissue ◽  
The Metabolic Syndrome ◽  
Artery Stiffness ◽  
Abdominal Lipectomy

Central (visceral) obesity is a key feature of the metabolic syndrome and an independent predictor of cardiovascular disease. Reux en Y gastric bypass (RnY) has been shown to offer protection against cardiovascular disease, but residual risk remains. It is also unknown whether the cardiovascular benefit is a consequence of a decrease in visceral (intra-abdominal) adipose tissue or of other factors. In this study, we compared the effects of RnY vs. removal of 90% of visceral adipose tissue (=5% body weight) by intra-abdominal lipectomy on cardiac function (echocardiography), macrovascular function (carotid artery stiffness) and microvascular function (coronary artery endothelium-dependent vasorelaxation) in a metabolic syndrome rat model (JCR:LA-cp, JCR). Cardiac output (CO) and ejection fraction (EF) were significantly decreased in JCR vs. normal (Sprague-Dawley, SD) rats (CO=50±5%, EF=45±2% of normal), and were significantly improved by both RnY and intra-abdominal lipectomy (CO=75±6%, EF=82±2% and CO=80±3%, EF=90±2% of normal, respectively). Likewise, acetylcholine-dependent coronary artery vasorelaxation was impaired in JCR rats (50±1% of normal), and was significantly improved by both RnY and intra-abdominal lipectomy (98±2% and 98±3% of normal, respectively). Carotid artery stiffness was significantly increased in JCR rats (~2 fold vs. SD), and was normalized by intra-abdominal lipectomy (to equal SD), but not by RnY (~2 fold vs. SD). Intra-abdominal lipectomy but not RnY also decreased cardiac and vascular elastin degradation in JCR rats (Lipectomy: ~50% (heart), ~75% (carotid); RnY: ~15% (heart), ~5% (carotid) vs. untreated JCR, respectively), concomitant with a decrease in matrix metalloproteinase 12 (MMP12), a major elastase, activation (~50% (heart), ~75% (carotid), ~87% (visceral fat), ~75% (circulating) vs. untreated JCR) and in 20-hydroxyeicosatetraeonic acid (20-HETE) levels (~4 (heart), ~7 (carotid), ~4 (visceral fat), ~4 (circulating) fold vs. untreated JCR). Thus, our data indicate that intra-abdominal adipose tissue itself is a source of factors that may be important negative regulators of micro- and macrovascular and cardiac function, but are not eliminated by RnY.

scholarly journals Visceral obesity, metabolic syndrome, insulin resistance and cancer

2011 ◽  
Vol 71 (1) ◽  
pp. 181-189 ◽  
Author(s):  
Suzanne L. Doyle ◽  
Claire L. Donohoe ◽  
Joanne Lysaght ◽  
John V. Reynolds
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Systemic Inflammation ◽  
Visceral Adipose Tissue ◽  
Tumour Progression ◽  
Visceral Adiposity ◽  
Oesophageal Adenocarcinoma ◽  
The Metabolic Syndrome ◽  
Visceral Adipose

This paper presents emerging evidence linking visceral adiposity and the metabolic syndrome (MetSyn) with carcinogenesis. The link between obesity and cancer has been clearly identified in a multitude of robust epidemiological studies. Research is now focusing on the role of visceral adipose tissue in carcinogenesis; as it is recognised as an important metabolic tissue that secretes factors that systemically alter the immunological, metabolic and endocrine milieu. Excess visceral adipose tissue gives rise to a state of chronic systemic inflammation with associated insulin resistance and dysmetabolism, collectively known as the MetSyn. Prospective cohort studies have shown associations between visceral adiposity, the MetSyn and increased risk of breast cancer, colorectal cancer and oesophageal adenocarcinoma. Furthermore, visceral adiposity and the MetSyn have been associated with increased tumour progression and reduced survival. The mechanisms by which visceral adiposity and the MetSyn are thought to promote tumorigenesis are manifold. These include alterations in adipokine secretion and cell signalling pathways. In addition, hyperinsulinaemia, subsequent insulin resistance and stimulation of the insulin-like growth factor-1 axis have all been linked with visceral adiposity and promote tumour progression. Furthermore, the abundance of inflammatory cells in visceral adipose tissue, including macrophages and T-cells, create systemic inflammation and a pro-tumorigenic environment. It is clear from current research that excess visceral adiposity and associated dysmetabolism play a central role in the pathogenesis of certain cancer types. Further research is required to elucidate the exact mechanisms at play and identify potential targets for intervention.

scholarly journals The metabolic syndrome is related to β3-adrenoceptor sensitivity in visceral adipose tissue

Diabetologia ◽  
1996 ◽  
Vol 39 (7) ◽  
pp. 838-860 ◽  
Author(s):  
J. Hoffstedt ◽  
H. Wahrenberg ◽  
A. Thörne ◽  
F. Lönnqvist
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
The Metabolic Syndrome ◽  
Visceral Adipose

Effect of voluntary exercise on peripheral tissue glucocorticoid receptor content and the expression and activity of 11β-HSD1 in the Syrian hamster

2006 ◽  
Vol 100 (5) ◽  
pp. 1483-1488 ◽  
Author(s):  
Agnes E. Coutinho ◽  
Jonathan E. Campbell ◽  
Sergiu Fediuc ◽  
Michael C. Riddell
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Enzyme Activity ◽  
Adipose Tissue ◽  
Protein Expression ◽  
Aerobic Exercise ◽  
Visceral Adipose Tissue ◽  
The Metabolic Syndrome ◽  
Visceral Adipose

Recent findings indicate that elevated levels of glucocorticoids (GC), governed by the expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and GC receptors (GR), in visceral adipose tissue and skeletal muscle lead to increased insulin resistance and the metabolic syndrome. Paradoxically, evidence indicates that aerobic exercise attenuates the development of the metabolic syndrome even though it stimulates acute increases in circulating GC levels. To investigate the hypothesis that training alters peripheral GC action to maintain insulin sensitivity, young male hamsters were randomly divided into sedentary (S) and trained (T) groups ( n = 8 in each). The T group had 24-h access to running wheels over 4 wk of study. In muscle, T hamsters had lower 11β-HSD1 protein expression (19.2 ± 1.40 vs. 22.2 ± 0.96 optical density, P < 0.05), similar 11β-HSD1 enzyme activity (0.9 ± 0.27% vs. 1.1 ± 0.26), and lower GR protein expression (9.7 ± 1.86 vs. 15.1 ± 1.78 optical density, P < 0.01) than S hamsters. In liver, 11β-HSD1 protein expression tended to be lower in T compared with S (19.2 ± 0.56 vs. 21.4 ± 1.05, P = 0.07), whereas both enzyme activity and GR protein expression were similar. In contrast, visceral adipose tissue contained ∼2.7-fold higher 11β-HSD1 enzyme activity in T compared with S (12.9 ± 3.3 vs. 4.8 ± 1.5% conversion, P < 0.05) but was considerably smaller in mass (0.24 ± 0.02 vs. 0.71 ± 0.06 g). Thus the intracellular adaptation of GC regulators to exercise is tissue specific, resulting in decreases in GC action in skeletal muscle and increases in GC action in visceral fat. These adaptations may have important implications in explaining the protective effects of aerobic exercise on insulin resistance and other symptoms of the metabolic syndrome.

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