scholarly journals Attenuation of cold stress-induced exacerbation of cardiac and adipose tissue pathology and metabolic disorders in a rat model of metabolic syndrome by the glucocorticoid receptor antagonist RU486

2016 ◽  
Vol 6 (4) ◽  
pp. e207-e207 ◽  
Author(s):  
K Nagasawa ◽  
N Matsuura ◽  
Y Takeshita ◽  
S Ito ◽  
Y Sano ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Glucocorticoid Receptor ◽  
Cold Stress ◽  
Receptor Antagonist ◽  
Rat Model ◽  
Metabolic Disorders ◽  
Antagonist Ru486

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.

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 Selective Glucocorticoid Receptor Antagonist CORT125281 Activates Brown Adipose Tissue and Alters Lipid Distribution in Male Mice

Endocrinology ◽  
2017 ◽  
Vol 159 (1) ◽  
pp. 535-546 ◽  
Author(s):  
Jan Kroon ◽  
Lisa L Koorneef ◽  
Jose K van den Heuvel ◽  
Cristy R C Verzijl ◽  
Nienke M van de Velde ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucocorticoid Receptor ◽  
Brown Adipose Tissue ◽  
Receptor Antagonist ◽  
Male Mice ◽  
Lipid Distribution ◽  
Brown Adipose

scholarly journals Shexiang Baoxin Pill Corrects Metabolic Disorders in a Rat Model of Metabolic Syndrome by Targeting Mitochondria

2018 ◽  
Vol 9 ◽  
Author(s):  
Dan Wei ◽  
Ningning Zheng ◽  
Lanyan Zheng ◽  
Leting Wang ◽  
Liang Song ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Rat Model ◽  
Metabolic Disorders ◽  
Shexiang Baoxin Pill

scholarly journals Stress hormones promote DNA damage in human oral keratinocytes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vitor Bonetti Valente ◽  
Diovana de Melo Cardoso ◽  
Giseli Mitsuy Kayahara ◽  
Giovana Barros Nunes ◽  
Kellen Cristine Tjioe ◽  
...  
Keyword(s):  
Dna Damage ◽  
Glucocorticoid Receptor ◽  
Receptor Antagonist ◽  
Stress Hormones ◽  
Oral Keratinocytes ◽  
Dna Breaks ◽  
Genotoxic Effects ◽  
Beta Adrenergic ◽  
Pre Treatment ◽  
Antagonist Ru486

AbstractChronic stress increases the systemic levels of stress hormones norepinephrine and cortisol. As well as tobacco-specific carcinogen NNK (4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone), they can induce expressive DNA damage contributing to the cancer development. However, it is unknown whether stress hormones have genotoxic effects in oral keratinocytes. This study investigated the effects of stress hormones on DNA damage in a human oral keratinocyte cell line (NOK-SI). NOK-SI cells stimulated with norepinephrine or cortisol showed higher DNA damage compared to untreated cells. Norepinephrine-induced DNA damage was reversed by pre-treatment with beta-adrenergic blocker propranolol. Cells treated with NNK combined to norepinephrine displayed reduced levels of caspases 3 and 7. Cortisol also reduced the activity of pro-apoptotic enzymes. NNK or norepinephrine promoted single-strand breaks and alkali-label side breaks in the DNA of NOK-SI cells. Pre-treatment of cells with propranolol abolished these effects. Carcinogen NNK in the presence or absence of cortisol also induced DNA damage of these cells. The genotoxic effects of cortisol alone and hormone combined with NNK were blocked partially and totally, respectively, by the glucocorticoid receptor antagonist RU486. DNA damage promoted by NNK or cortisol and carcinogen combined to the hormone led to intracellular γH2AX accumulation. The effects caused by NNK and cortisol were reversed by propranolol and glucocorticoid receptor antagonist RU486, respectively. Propranolol inhibited the oxidation of basis induced by NNK in the presence of DNA-formamidopyrimidine glycosylase. DNA breaks induced by norepinephrine in the presence or absence of NNK resulted in higher 8OHdG cellular levels. This effect was also induced through beta-adrenergic receptors. Together, these findings indicate that stress hormones induce DNA damage of oral keratinocytes and could contribute to oral carcinogenesis.

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