The prebiotic fiber inulin ameliorates cardiac, adipose tissue, and hepatic pathology but exacerbates hypertriglyceridemia in rats with metabolic syndrome

2020 ◽  
Author(s):  
Yuki Komatsu ◽  
Kiyoshi Aoyama ◽  
Mamoru Yoneda ◽  
Sao Ashikawa ◽  
Shiho Nakano ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Dietary Fiber ◽  
Metabolic Disorders ◽  
Regulatory Element ◽  
Left Ventricular ◽  
Soluble Fiber ◽  
High Fiber ◽  
Obese Rats ◽  
Hepatic Pathology

Prebiotics ameliorate dysbiosis and influence metabolism and the immune system, but their effects on cardiovascular complications in metabolic disorders remain largely unknown. We here investigated the effects of the soluble fiber inulin on cardiac, adipose tissue, and hepatic pathology as well as on metabolic disorders in DahlS.Z-Leprfa/Leprfa (DS/obese) rats, an animal model of metabolic syndrome (MetS). DS/obese rats and their homozygous lean (DahlS.Z-Lepr+/Lepr+, or DS/lean) littermate controls were fed a purified diet containing 5% or 20% inulin from 9 to 13 weeks of age. The high-fiber diet ameliorated hypertension, left ventricular inflammation, fibrosis, and diastolic dysfunction, attenuated adipose tissue inflammation and fibrosis as well as alleviated the elevation of interleukin-6 levels, without affecting insulin resistance, in DS/obese rats. In addition, high fiber intake ameliorated lipid accumulation, inflammation, and fibrosis, attenuated the reduction in AMPK activity and the up-regulation of sterol regulatory element binding protein-1c gene expression, and further increased the expression of microsomal triglyceride transfer protein gene, in the liver of DS/obese rats. It also mitigated increases in total and non-high-density lipoprotein-cholesterol levels but increased the triglyceride concentration in serum in these rats. None of these parameters was affected by high dietary fiber in DS/lean rats. The proportion of regulatory T cells in adipose tissue was influenced by dietary fiber but not by genotype. Our results indicate that inulin exacerbates hypertriglyceridemia but alleviates hypertension and cardiac injury as well as adipose tissue and hepatic pathology in MetS rats.

Restraint stress exacerbates cardiac and adipose tissue pathology via β-adrenergic signaling in rats with metabolic syndrome

2015 ◽  
Vol 308 (10) ◽  
pp. H1275-H1286 ◽  
Author(s):  
Natsumi Matsuura ◽  
Kai Nagasawa ◽  
Yuji Minagawa ◽  
Shogo Ito ◽  
Yusuke Sano ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Restraint Stress ◽  
Metabolic Disorders ◽  
Subcutaneous Fat ◽  
Left Ventricular ◽  
Zucker Rats ◽  
Chronic Restraint Stress ◽  
Obese Rats

Restraint stress stimulates sympathetic nerve activity and can affect adiposity and metabolism. However, the effects of restraint stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS) have remained unclear. We investigated the effects of chronic restraint stress and β-adrenergic receptor (β-AR) blockade on cardiac and adipose tissue pathology and metabolic disorders in a rat model of MetS. DahlS.Z- Leprfa/ Leprfa (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats. Rats were exposed to restraint stress (restraint cage, 2 h/day) for 4 wk from 9 wk of age with or without daily subcutaneous administration of the β-AR blocker propranolol (2 mg/kg). Age-matched homozygous lean littermates of DS/obese rats (DahlS.Z- Lepr+ /Lepr+ rats) served as control animals. Chronic restraint stress exacerbated hypertension as well as left ventricular hypertrophy, fibrosis, diastolic dysfunction, and oxidative stress in a manner sensitive to propranolol treatment. Restraint stress attenuated body weight gain in DS/obese rats, and this effect tended to be reversed by propranolol ( P = 0.0682). Restraint stress or propranolol did not affect visceral or subcutaneous fat mass. However, restraint stress potentiated cardiac and visceral adipose tissue inflammation in DS/obese rats, and these effects were ameliorated by propranolol. Restraint stress also exacerbated glucose intolerance, insulin resistance, and abnormal lipid metabolism in a manner sensitive to propranolol. In addition, restraint stress increased urinary norepinephrine excretion, and propranolol attenuated this effect. Our results thus implicate β-ARs in the exacerbation of cardiac and adipose tissue pathology and abnormal glucose and lipid metabolism induced by restraint stress in this model of MetS.

Abstract 278: The Glucocorticoid Receptor Antagonist RU486 Ameliorates Cold Stress-induced Exacerbation of Cardiac and Adipose Tissue Pathology and Metabolic Disorders in a Rat Model of Metabolic Syndrome

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Kai Nagasawa ◽  
Natsumi Matsuura ◽  
Yuji Minagawa ◽  
Shogo Ito ◽  
Yusuke Sano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Cold Stress ◽  
Rat Model ◽  
Metabolic Disorders ◽  
Glucose And Lipid Metabolism ◽  
Obese Rats ◽  
Antagonist Ru486

Introduction: Chronic stress, when combined with hyperphagia, can affect adiposity and metabolism. However, few studies have reported the effects of cold stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS). We investigated the effects of chronic cold stress and glucocorticoid receptor (GR) blockade on cardiac and adipose tissue pathology and gene expression and on glucose and lipid metabolism in a rat model of MetS. Methods and Results: We used DahlS.Z-Leprfa/Leprfa (DS/obese) rats which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a new animal model of MetS. DS/obese rats were exposed to cold stress (ice-cold water, 1 cm depth, 2 h/day) for 4 weeks beginning at 9 weeks of age with or without the GR antagonist RU486 (2 mg/kg/day, sc). Age-matched homozygous lean (DahlS.Z-Lepr+/Lepr+, or DS/lean) littermates of DS/obese rats served as controls. Chronic cold stress exacerbated hypertension as well as left ventricular (LV) hypertrophy, fibrosis and diastolic dysfunction, in a manner sensitive to RU486. Cold stress and RU486 did not affect body weight or visceral and subcutaneous fat mass. In contrast, cold stress further increased superoxide production and NADPH oxidase activity in the heart as well as macrophage infiltration and the expression of proinflammatory genes in LV and visceral fat tissue. RU486 treatment inhibited these changes in gene expression, as well as cardiac oxidative stress and inflammation and adipose tissue inflammation. Cold stress further up-regulated cardiac renin-angiotensin-aldosterone system gene expression as well as the expression of GR and 11β-hydroxysteroid dehydrogenase type 1 genes in LV and visceral adipose tissue, and all of these effects were attenuated by RU486. In addition, RU486 ameliorated the stress-induced deterioration of dyslipidemia (elevations in low-density lipoprotein cholesterol, triglycerides, and free fatty acid) as well as that of glucose intolerance and insulin resistance. Conclusions: The present results indicate that GRs may be involved in cold stress-induced exacerbation of cardiac and adipose tissue pathology as well as that of glucose and lipid metabolism in a rat model of MetS.

Abstract 1125: Mulberry Leaf Ameliorates The Production Of Adipocytokines By Inhibiting Oxidative Stress In White Adipose Tissue In db/db Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Masayuki Sugimoto ◽  
Hidenori Arai ◽  
Yukinori Tamura ◽  
Toshinori Murayama ◽  
Koh Ono ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Metabolic Disorders ◽  
The Body ◽  
Mulberry Leaf ◽  
The Metabolic Syndrome ◽  
Pparγ Agonist ◽  
Tnf Α

Mulberry leaf (ML) is commonly used to feed silkworms. Previous study showed that ML ameliorates atherosclerosis. However, its mechanism is not completely understood. Because dysregulated production of adipocytokines is involved in the development of the metabolic syndrome and cardiovascular disease, we examined the effect of ML on the production of adipocytokines and metabolic disorders related to the metabolic syndrome, and compared its effect with that of a PPARγ agonist, pioglitazone (Pio). By treating obese diabetic db/db mice with ML, Pio, and their combination, we investigated the mechanism by which they improve metabolic disorders. In this study, db/+m (lean control) and db/db mice were fed a standard diet with or without 3% (w/w) ML and/or 0.01% (w/w) Pio for 12 weeks from 9 weeks of age. At the end of the experiment we found that ML decreased plasma glucose and triglyceride by 32% and 30%, respectively. Interestingly, administration of ML in addition to Pio showed additive effects; further 40% and 30% reduction in glucose and triglyceride compared with Pio treatment, respectively. Moreover, administration of ML in addition to Pio suppressed the body weight increase by Pio treatment and reduced visceral/subcutaneous fat ratio by 20% compared with control db/db mice. Importantly, ML treatment increased expression of adiponectin in white adipose tissue (WAT) by 40%, which was only found in db/db mice, not in control db/+m mice. Combination of ML and Pio increased plasma adiponectin concentrations by 25% and its expression in WAT by 17% compared with Pio alone. In contrast, ML decreased expression of TNF-α and MCP-1 by 25% and 20%, respectively, and the addition of Pio resulted in a further decrease of these cytokines by about 45%. To study the mechanism, we examined the role of oxidative stress. ML decreased the amount of lipid peroxides by 43% and the expression of NADPH oxidase subunits in WAT, which was consistent with the results of TNF-α and MCP-1. Thus our results indicate that ML ameliorates adipocytokine dysregulation by inhibiting oxidative stress in WAT of obese mice, and that ML may have a potential for the treatment of the metabolic syndrome as well as reducing adverse effects of Pio.

scholarly journals Electroacupuncture Decreases the Leukocyte Infiltration to White Adipose Tissue and Attenuates Inflammatory Response in High Fat Diet-Induced Obesity Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Chorng-Kai Wen ◽  
Tzung-Yan Lee
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Response ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Regulatory Element ◽  
Epididymal Adipose Tissue ◽  
High Fat ◽  
Obese Rats

Suppression of white adipose tissue inflammatory signaling may contribute to the pathogenesis of obesity-induced inflammatory response. However, the precise mechanism of efficacy of acupuncture related to adipose tissue remains poorly understood. In the present study we evaluated the anti-inflammatory activities of 10 Hz electroacupuncture (EA) which was applied at the acupoint Zusanli (ST36) for 20 min per day in high-fat diet- (HFD-) induced obesity model. Treatment lasted for one week. Obese rats treated with EA showed significantly reduced body weight compared with the rats in HFD group. EA decreased the number of F4/80 and CD11b-positive macrophages in epididymal adipose tissue. We found that 10 Hz EA given 7 days/week at ST36 acupoints significantly alleviated macrophage recruitment and then improved the obesity-associated factors of sterol regulatory element-binding protein-1 (SREBP-1) and target genes expression in rats with HFD. Adipose tissue inflammatory responses indicated by tumor necrosis factor-α(TNF-α), IL-6, monocyte chemotactic protein-1 (MCP-1), and CD68 mRNA expression were significantly reduced by EA in obese rats. Additionally, EA was found to significantly reduced serum levels of TNF-α, IL-6, and IL-1 in this model. These results indicated that EA improved adipose tissue inflammatory response in obese rats, at least partly, via attenuation of lipogenesis signaling.

A Sodium Glucose Cotransporter 2 Inhibitor Fails to Improve Perivascular Adipose Tissue-Mediated Modulation of Vasodilation and Cardiac Function in Rats With Metabolic Syndrome

2021 ◽  
pp. 107424842110018
Author(s):  
Satomi Kagota ◽  
Kana Maruyama-Fumoto ◽  
John J. McGuire ◽  
Kazumasa Shinozuka
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Cardiac Function ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Organ Bath ◽  
Perivascular Adipose Tissue ◽  
Treatment Groups ◽  
Glucose Levels ◽  
Serum And Urine

Arterial perivascular adipose tissue (PVAT) can elicit vasodilator signals complementary to those elicited by the endothelium in SHRSP.Z- Leprfa/IzmDmcr (SHRSP.ZF) rats, an animal model of metabolic syndrome (MetS). Here, we tested whether a glucose cotransporter 2 inhibitor (SGLT2-i; tofogliflozin) increased this PVAT effect to prevent the deterioration of cardiac function in aging SHRSP.ZF rats. Tofogliflozin treatments (1 or 10 mg/kg/day) or vehicle (control) were administered for 10 weeks by oral gavage to SHRSP.ZF rats, starting at 13 weeks of age. At 23 weeks of age, glucose levels in the serum and urine (24 h after the last administration) were determined using commercial kits. Vasodilator responsiveness of PVAT-surrounded or PVAT-free superior mesenteric arteries was determined using acetylcholine with organ-bath methods. Cardiac ventricular function and coronary flow were determined using Langendorff heart preparations. Serum and urine glucose levels in SGLT2-i treatment groups did not differ from those in the controls, but the ratios of glycated to non-glycated albumin were lower than those in the controls. Tofogliflozin treatments did not alter relaxations in the presence of PVAT or affect relaxations of PVAT-free arteries. Left ventricular systolic pressures, maximum rate of pressure decline, and coronary flow in ex vivo hearts did not differ among the treatment groups. PVAT effects and cardiac dysfunction were not altered by tofogliflozin treatment in SHRSP.ZF rats with MetS. These results do not provide strong evidence to support the use of SGLT2-i as a cardiovascular protective therapy in MetS, which occurs prior to the onset of type 2 diabetes.

scholarly journals The relationship of risk factors and heart remodeling in patients with metabolic syndrome and arterial hypertension

2021 ◽  
pp. 19-25
Author(s):  
E. L. Polozova ◽  
E. V. Puzanova ◽  
A. A. Seskina ◽  
N. S. Nefedov
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Left Ventricular Hypertrophy ◽  
Arterial Hypertension ◽  
Cardiac Remodeling ◽  
Ventricular Hypertrophy ◽  
Metabolic Disorders ◽  
Clinical Analysis ◽  
Left Ventricular ◽  
Cardiology Department

Introduction. Arterial hypertension (AH) is a widespread disease in the population of the world. It also acts as one of the constituent components of metabolic syndrome (MS), which is a global “epidemic” of our time. Target organs in such patients are affected much earlier and their changes are more pronounced than in hypertensive patients without metabolic disorders. It is important to study the contribution of risk factors to the progression of cardiac dysfunction in this category of patients.Purpose of the study. To study the influence of risk factors on heart remodeling in patients with hypertension, burdened and not burdened by metabolic disorders, selected for clinical analysis from the cardiology department of the Republican Clinical Hospital № 4, Saransk in 2016-2019.Materials and methods. For clinical analysis, 139 patients were selected from the cardiology department of the Republican Clinical Hospital No. 4, Saransk. Depending on the presence of metabolic disorders, the following groups were identified: Group I (n = 72) – patients with MS and AH; Group II (n = 67) – AH patients without metabolic disorders. The study evaluated the morphological and functional state of the myocardium and risk factors in the analyzed groups.Results. In the group of patients with hypertension, aggravated by metabolic disorders, more pronounced processes of cardiac remodeling were revealed. It has been shown that patients with MS develop both eccentric and concentric models of left ventricular hypertrophy. The influence of the level of blood pressure and body mass index is differently reflected on the type of restructuring of the geometry of the myocardium. Patients with hypertension combined with metabolic disorders have a wider prevalence of risk factors. The burden of risk factors is higher in patients with concentric left ventricular hypertrophy and MS.Conclusions. The role of metabolic disorders in the mechanism of cardiac remodeling development in patients with hypertension in combination with MS was determined. 

scholarly journals Metabolic Syndrome Mediates ROS-miR-193b-NFYA-Dependent Down Regulation of sGC and Contributes to Exercise-Induced Pulmonary Hypertension in HFpEF

Circulation ◽  
2021 ◽  
Author(s):  
Taijyu Satoh ◽  
Longfei Wang ◽  
Cristina Espinosa-Diez ◽  
Bing Wang ◽  
Scott A. Hahn ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Pulmonary Hypertension ◽  
Vascular Dysfunction ◽  
Sglt2 Inhibitor ◽  
Left Ventricular ◽  
Mitochondrial Ros ◽  
Obese Rats ◽  
Cgmp Signaling ◽  
Exercise Induced ◽  
Pulmonary Vascular Dysfunction

Background: Many patients with heart failure with preserved ejection fraction (HFpEF) have metabolic syndrome and develop exercise-induced pulmonary hypertension (EIPH). Increases in pulmonary vascular resistance in patients with HFpEF portend a poor prognosis; this phenotype is referred to as combined pre-and post-capillary PH (CpcPH). Therapeutic trials for EIPH and CpcPH have been disappointing, suggesting the need for strategies that target upstream mechanisms of disease. This work reports novel rat EIPH models and mechanisms of pulmonary vascular dysfunction centered around the transcriptional repression of the soluble guanylate cyclase (sGC) enzyme in pulmonary artery smooth muscle cells (PAVSMCs). Methods: We used obese ZSF-1 leptin-receptor knock-out rats (HFpEF model), obese ZSF-1 rats treated with SU5416 to stimulate resting PH (Obese+sugen, CpcPH model), and Lean ZSF-1 rats (controls). Right and left ventricular hemodynamics were evaluated via implanted-catheters during treadmill exercise. PA function was evaluated using MRI and myography. Overexpression of NFYA, a transcriptional-enhancer of sGCβ1, was performed by PA delivery of adeno-associated-virus 6 (AAV6). Treatment groups received SGLT2 inhibitor Empagliflozin in drinking water. PAVSMCs from rats and humans were cultured with Palmitic acid, Glucose, and Insulin (PGI) to induce metabolic-stress. Results: Obese rats showed normal resting right ventricular systolic pressures (RVSP) which significantly increased during exercise, modeling EIPH. Obese+sugen rats showed anatomical PA remodeling and developed elevated RVSP at rest, which was exacerbated with exercise, modeling CpcPH. Myography and MRI during dobutamine-challenge revealed PA functional impairment of both obese groups. PAs of obese rats produced reactive oxygen species (ROS) and decreased sGCβ1 expression. Mechanistically, cultured PAVSMCs from obese rats, humans with diabetes or treated with PGI, showed increased mitochondrial-ROS, which enhanced miR-193b-dependent RNA-degradation of NFYA, resulting in decreased sGCβ1-cGMP signaling. Forced NYFA expression by AAV6 delivery increased sGCβ1 levels and improved exercise-PH in Obese+sugen rats. Treatment of Obese+sugen rats with Empagliflozin improved metabolic syndrome, reduced mitochondrial ROS and miR-193b levels, restored NFYA/sGC activity, and prevented EIPH. Conclusions: In HFpEF and CpcPH models, metabolic syndrome contributes to pulmonary vascular dysfunction and EIPH through enhanced ROS and miR-193b expression, which down-regulates NFYA-dependent sGCβ1 expression. AAV-mediated NFYA overexpression and SGLT2 inhibition restores NFYA-sGCβ1-cGMP signaling and ameliorates EIPH.

Hemodynamic effects of weight reduction in the obese rat

1984 ◽  
Vol 247 (2) ◽  
pp. R266-R271
Author(s):  
D. L. Crandall ◽  
B. M. Goldstein ◽  
R. A. Gabel ◽  
P. Cervoni
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Body Weight ◽  
Adipose Tissue ◽  
Cardiac Output ◽  
Weight Reduction ◽  
Left Ventricular ◽  
Tissue Blood Flow ◽  
Arterial Blood ◽  
Obese Rats

The effect of defined increments of weight loss on hemodynamics has been investigated in conscious, unrestrained, spontaneously obese rats. Obese rats were subjected to a calorically restricted diet and were used for experimentation on achieving a 10, 20, or 30% reduction in body weight. After monitoring resting blood pressure and heart rate, radioactive microspheres were infused for determination of blood flow distribution. Of 10 organs sample, only heart, liver, kidneys, and 2 adipose tissue depots exhibited significant decreases in weight associated with body weight reduction. Mean arterial blood pressure remained unchanged, while stroke volume, left ventricular work, and cardiac output decreased significantly. Blood flow decreased to kidneys, testes, and adipose tissue through a 30% reduction in body weight, but the fractional distribution of cardiac output decreased only to adipose tissue. Therefore the large decreases in renal and adipose tissue blood flow during weight reduction may contribute to the associated decrease in cardiac output. Of those vascular beds examined, however, both absolute and relative blood flow decreased only to adipose tissue, thus denoting the influence of fat mass on hemodynamics during obesity.

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