Glucocorticoid-Induced Metabolic Disturbances are Exacerbated in Obesity

Harvey, Innocence; Stephenson, Erin J.; Redd, JeAnna R.; Tran, Quynh; Hochberg, Irit; Qi, Nathan; Bridges, Dave

doi:10.1101/184507

Cited by 2 publications

(2 citation statements)

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“…The accumulation of lipid droplets was also observed on day 28 in Group B. Similar results were reported by other groups [ 28 - 31 ] stating that the chronic elevations in GCs may be associated with increased incorporation of liver fat. GCs stimulate hepatic gluconeogenesis and increase the hepatic synthesis and storage of glycogen in the liver [ 30 ].…”

Section: Discussionsupporting

confidence: 90%

Effects of steroid growth promoter on morphological and biochemical adaptations in liver of broiler

2020

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Aim: The study was conducted to observe the effects of dexamethasone (DEX) on the gross study and histomorphometry of liver and on the alterations of biochemical parameters of broilers. Materials and Methods: Ninety day-old chicks were collected and assigned to one of three groups: The control, Group A, and Group B. The control, Group A, and Group B were fed for 28 days with a homemade ration, a commercial broiler type ration, and a homemade ration with DEX (7 mg/kg feed), respectively. Liver samples were collected from the individual birds after sacrificing on days 7, 14, 21, and 28 of the experiment. Morphometric characteristics (length, weight, color, and texture) of the liver were examined. Histomorphological alterations of the liver were assessed with routine hematoxylin and eosin staining. To measure the biochemical parameters, blood samples were collected on days 7, 14, 21, and 28 of the experiment. Liver function test was performed spectrophotometrically by analyzing serum biochemical markers, that is, alanine aminotransferase (ALT), aspartate aminotransferase, and alkaline phosphatase (ALP). Thin-layer chromatography (TLC) was performed for the detection of hepatic steroids. Results: Hemorrhagic and congested livers were found in broilers of Group B. There were no significant changes found in weight and length of the livers; only numerical decrease in weight and length was observed in birds of Group B. Liver width was increased in Group B on day 21. Histological observation of livers showed accumulation of lipid droplets, congestion of the sinusoids, and central veins in broilers of Group B. Biochemical analyses showed increased levels of ALT in Group B as compared to Group A on day 14 of the experiment. TLC evaluation revealed a positive result in Group B on 28 days of the experiment. Conclusion: The present study results show that DEX may alter the liver morphology and the concentration of ALT in the circulation of broilers.

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Section: Discussionsupporting

confidence: 90%

Effects of steroid growth promoter on morphological and biochemical adaptations in liver of broiler

2020

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“…In rodents, dexamethasone and corticosterone both cause insulin resistance and muscle atrophy (8)(9)(10). Corticosterone induces adiposity, but the effect of dexamethasone on body composition is not as clear, as both loss and gain of total fat mass have been reported (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone-associated metabolic effects in male mice are partially caused by depletion of endogenous corticosterone

et al. 2022

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Synthetic glucocorticoids are clinically used to treat auto-immune and inflammatory disease. Despite the high efficacy, glucocorticoid treatments causes side effects such as obesity and insulin resistance in many patients. Via their pharmacological target, the glucocorticoid receptor (GR), glucocorticoids suppress endogenous glucocorticoid secretion. Endogenous, but not synthetic, glucocorticoids activate the mineralocorticoid receptor (MR) and side effects of synthetic glucocorticoids may thus not only result from GR hyperactivation but also from MR hypoactivation. Here, we tested the hypothesis that reactivation of MR with corticosterone add-on treatment can attenuate the metabolic effects of the synthetic glucocorticoid dexamethasone. Male 8-week-old C57Bl/6J mice received a high-fat diet supplemented with dexamethasone or vehicle, and were subcutaneously implanted with low-dose corticosterone- or vehicle-containing pellets. Dexamethasone strongly reduced body weight and fat mass gain, while corticosterone add-on partially normalized this. Dexamethasone-induced hyperglycemia and hyperinsulinemia were exacerbated by corticosterone add-on, which was prevented by MR antagonism. In subcutaneous white adipose tissue, corticosterone add-on prevented the dexamethasone-induced expression of intracellular lipolysis genes. In brown adipose tissue, dexamethasone also upregulated gene expression of brown adipose tissue identity markers, lipid transporters and lipolysis enzymes, which was prevented by corticosterone add-on. In conclusion, corticosterone add-on treatment prevents several, while exacerbating other metabolic effects of dexamethasone. While the exact role of MR remains elusive, this study suggests that corticosterone suppression by dexamethasone contributes to its effects in mice.

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Glucocorticoid-Induced Metabolic Disturbances are Exacerbated in Obesity

Cited by 2 publications

References 46 publications

Effects of steroid growth promoter on morphological and biochemical adaptations in liver of broiler

Effects of steroid growth promoter on morphological and biochemical adaptations in liver of broiler

Dexamethasone-associated metabolic effects in male mice are partially caused by depletion of endogenous corticosterone

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