2007
DOI: 10.1210/en.2007-1214
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Effect of Dexamethasone on Glucose Tolerance and Fat Metabolism in a Diet-Induced Obesity Mouse Model

Abstract: Prolonged exposure to elevated glucocorticoid levels is known to produce insulin resistance (IR), a hallmark of diabetes mellitus. Although not fully elucidated, the underlying molecular mechanisms by which glucocorticoids induce IR may provide potential targets for pharmacological interventions. Here we characterized muscle lipid metabolism in a dexamethasone-aggravated diet-induced obesity murine model of IR. Male C57BL/6 mice on a high-fat diet for 2 months when challenged with dexamethasone showed elevated… Show more

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Cited by 76 publications
(48 citation statements)
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“…Importantly, diet-induced obese mice are the most commonly used model for the study of polygenic obesity, as these mice share numerous features of obese patients. Although the effects of a high-fat diet in combination with a history of CVS are unknown, it is well established that chronic-restraint stress in rodents has a synergistic action on the HPA axis that translates into altered lipid metabolism and can lead to insulin resistance [24,40]. Increased activity of the HPA axis with higher levels of circulating glucocorticoids opposes insulin action [41,42], thereby potentially predisposing the organism to insulin resistance and its consequences.…”
Section: Discussionmentioning
confidence: 99%
“…Importantly, diet-induced obese mice are the most commonly used model for the study of polygenic obesity, as these mice share numerous features of obese patients. Although the effects of a high-fat diet in combination with a history of CVS are unknown, it is well established that chronic-restraint stress in rodents has a synergistic action on the HPA axis that translates into altered lipid metabolism and can lead to insulin resistance [24,40]. Increased activity of the HPA axis with higher levels of circulating glucocorticoids opposes insulin action [41,42], thereby potentially predisposing the organism to insulin resistance and its consequences.…”
Section: Discussionmentioning
confidence: 99%
“…However, it has been shown in the animal model, that dexamethasone treatment impairs glucose tolerance and is associated with perturbation of lipid metabolism. 42 In addition to its stimulating effect on expression of proinflammatory cytokines in macrophages, activin A is positioned as a profibrotic factor in adipose tissue of obese patients. 37 Therefore, a question that should be addressed is related to the phenotype of adipocyte progenitors under conditions leading to the increase activity of activin A?…”
Section: Regulators Of Activin Expressionmentioning
confidence: 99%
“…However, particularly when given at higher doses and for extended periods of time, glucocorticoids are associated with multiple and potentially debilitating adverse outcomes, which are often chronic in nature and difficult to treat. These include, but are not limited to, musculoskeletal pathologies such as osteoporosis (4) and sarcopenia (5); metabolic disorders such as glucose intolerance, diabetes mellitus, and dyslipidemia (6,7); and excessive and abnormal fat accrual (6).…”
Section: Introductionmentioning
confidence: 99%