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

Chronic stress affects the central nervous system as well as endocrine, metabolic and immune systems. However, the effects of cold stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS) have remained unclear. We recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats,...

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Published in:Nutrition & diabetes 2016-04, Vol.6 (4), p.e207-e207
Main Authors: Nagasawa, K, Matsuura, N, Takeshita, Y, Ito, S, Sano, Y, Yamada, Y, Uchinaka, A, Murohara, T, Nagata, K
Format: Article
Language:English
Subjects:
11-beta-Hydroxysteroid Dehydrogenase Type 1 - metabolism
Adipose Tissue - drug effects
Adipose Tissue - pathology
Animals
Cold Temperature
Disease Models, Animal
Fibrosis - drug therapy
Glucose Intolerance
Heart - drug effects
Heart - physiopathology
Hypertrophy, Left Ventricular - drug therapy
Hypertrophy, Left Ventricular - metabolism
Male
Metabolic Syndrome - drug therapy
Mifepristone - pharmacology
Original
Rats
Rats, Inbred Dahl
Rats, Zucker
Receptors, Glucocorticoid - antagonists & inhibitors
Receptors, Glucocorticoid - metabolism
Receptors, Leptin - metabolism
Stress, Physiological - drug effects
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Summary:Chronic stress affects the central nervous system as well as endocrine, metabolic and immune systems. However, the effects of cold stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS) have remained unclear. We recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of MetS. We have now investigated the effects of chronic cold stress and glucocorticoid receptor (GR) blockade on cardiac and adipose tissue pathology as well as on metabolic parameters in this model. DS/obese rats were exposed to cold stress (immersion in ice-cold water to a depth of 1-2 cm for 2 h per day) with or without subcutaneous injection of the GR antagonist RU486 (2 mg kg(-1)day(-1)) for 4 weeks beginning at 9 weeks of age. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+)) littermates served as a control. Chronic cold stress exacerbated hypertension as well as left ventricular (LV) hypertrophy, fibrosis and diastolic dysfunction in DS/obese rats in a manner sensitive to RU486 treatment. Cold stress with or without RU486 did not affect body weight or fat mass. In contrast, cold stress further increased cardiac oxidative stress as well as macrophage infiltration and proinflammatory gene expression in LV and visceral fat tissue, with all of these effects being attenuated by RU486. Cold stress also further increased GR and 11β-hydroxysteroid dehydrogenase type 1 mRNA and protein abundance in LV and visceral adipose tissue, and these effects were again inhibited by RU486. In addition, RU486 ameliorated the stress-induced aggravation of dyslipidemia, glucose intolerance and insulin resistance in DS/obese rats. Our results implicate GR signaling in cold stress-induced exacerbation of cardiac and adipose tissue pathology as well as of abnormal glucose and lipid metabolism in a rat model of MetS.
ISSN:2044-4052
2044-4052
DOI:10.1038/nutd.2016.14