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.

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.

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.

scholarly journals Identification of Novel GH-Regulated Pathway of Lipid Metabolism in Adipose Tissue: A Gene Expression Study in Hypopituitary Men

2011 ◽  
Vol 96 (7) ◽  
pp. E1188-E1196 ◽  
Author(s):  
Jing Ting Zhao ◽  
Mark J. Cowley ◽  
Paul Lee ◽  
Vita Birzniece ◽  
Warren Kaplan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Gene Expression Study ◽  
Expression Study

scholarly journals Adipose-tissue-specific increase in glyceraldehyde-3-phosphate dehydrogenase activity and mRNA amounts in suckling pre-obese Zucker rats. Effect of weaning

1988 ◽  
Vol 254 (2) ◽  
pp. 483-487 ◽  
Author(s):  
I Dugail ◽  
A Quignard-Boulange ◽  
R Bazin ◽  
X Le Liepvre ◽  
M Lavau
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Zucker Rats ◽  
Tissue Specific ◽  
Gapdh Gene ◽  
Gapdh Activity ◽  
Weanling Rats ◽  
Obese Rats ◽  
Specific Increase ◽  
Obese Zucker Rats

The regulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression was studied during the onset of obesity in the genetically obese (fa/fa) rat by determination of GAPDH activity and hybridizable mRNA amounts in adipose tissue and liver from suckling and weanling rats. GADPH activity remained low throughout the suckling period, and a burst of activity occurred after weaning in both lean and obese pups. As early as 7 days of age, adipose tissue from pre-obese rats displayed a significant increase in enzyme activity, whereas no difference could be detected in the liver. In both suckling (16 days of age) and weanling (30 days of age) obese rats a proportionate increase in GAPDH activity and mRNA amounts was observed in adipose tissue, but not in liver. It is concluded that the obese genotype influences GAPDH gene expression at a pretranslational level and in a tissue-specific manner. This phenomenon could partly contribute to the hyperactive fat accretion in the obese rat, since glycolysis is the major metabolic pathway for lipogenic substrates in adipose tissue.

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