Chronic glucocorticoid treatment enhances lipogenic activity in visceral adipocytes of male Wistar rats

Chimin, Patrícia; Farias, Talita da Silva Mendes de; Leal, Francisco; Lopes, Andressa Bolsoni; Campaña, Amanda Baron; Andreotti, Sandra; Lima, Fábio Bessa

doi:10.1111/apha.12226

Cited by 44 publications

(39 citation statements)

References 37 publications

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“…In fact, the lower dose (0.1 mg ml −1 ) also induced adrenal atrophy without any significant effect on corticosterone serum levels detected at the end of the treatment. This lack of effect on corticosteronaemia could be related to the measurements of corticorsterone serum levels (Bowles et al, 2015;Chimin et al, 2014;Ferrau & Korbonits, 2015;Gasparini et al, 2016;Kong et al, 2015;Ramage et al, 2016;Sefton et al, 2016;van den Beukel et al, 2015). Our model accords with this as we observed body weight loss, increased adiposity, insulin resistance and dyslipidaemia.…”

Section: Discussionsupporting

confidence: 81%

Brown adipose tissue remodelling induced by corticosterone in male Wistar rats

Mousovich-Neto

Matos

Costa

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?Does glucocorticoid excess disrupt brown adipose tissue (BAT) phenotype and function? What is the main finding and its importance?Glucocorticoid excess induced an extensive remodelling of interscapular BAT, resulting in a white‐like phenotype in association with metabolic disturbances. Glucocorticoids might be an important modulator of BAT physiology and BAT may have a role in pathophysiology of metabolic disturbances induced by glucocorticoid excess. Abstract In mammals, brown adipose tissue (BAT) is centrally involved in energy metabolism. To test the hypothesis that glucocorticoid excess disrupts BAT phenotype and function, male Wistar rats were treated with corticosterone in drinking water for 21 days. To confirm induction of glucocorticoid excess and metabolic disturbances, adrenal weight, corticotrophin releasing hormone mRNA levels and corticosterone serum levels were measured and a glucose tolerance test and serum triacylglycerol analyses were performed. Adipose tissue deposits were excised, weighed and evaluated by a set of biochemical, histological and molecular procedures, including thin‐layer chromatography, histochemistry, immunohistochemistry, quantitative real‐time polymerase chain reaction, high‐resolution oxygraphy, ATP synthesis and enzymatic activity measurements. The approach was successful in induction of glucocorticoid excess and metabolic disturbances. Lower body weight and increased adiposity were observed in corticosterone‐treated rats. Interscapular brown adipose tissue (iBAT) showed higher sensitivity to glucocorticoids than other fat deposits. The treatment induced lipid accumulation, unilocular rearrangement, increased collagen content and decreased innervation in iBAT. Furthermore, expression of Prdm16 (P < 0.05), Ucp1 (P <0.05) and Slc7a10 (P <0.05) mRNA decreased, while expression of Fasn (P <0.05) and Lep (P <0.05) mRNA increased in brown adipose tissue. Also, the levels of UCP1 diminished (P <0.001, 2.5‐fold). Finally, lower oxygen consumption (P <0.05), ATP synthesis (P <0.05) and mitochondrial content (P <0.05) were observed in iBAT of glucocorticoid‐treated rats. Glucocorticoid excess induced an extensive remodelling of interscapular brown adipose tissue, resulting in a white‐like phenotype in association with metabolic disturbances.

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Section: Discussionsupporting

confidence: 81%

Brown adipose tissue remodelling induced by corticosterone in male Wistar rats

Mousovich-Neto

Matos

Costa

et al. 2019

Experimental Physiology

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“…This reduced body mass in the GC-treated rats is partially explained by their hypophagic behavior, which was evident on the third day of dexamethasone treatment in both male groups and in the 3-month-old female rats, and was obvious at the end of treatment in all of the groups. GC-induced hypophagy may be a result of anorexigenic insulin and leptin effects on the hypothalamus, as the concentration of both hormones is elevated in adult dexamethasone-treated rats (Rafacho et al 2008aChimin et al 2014). There is evidence for increased plasma insulin and leptin values (Caldefie-Chézet et al 2001) in young (3 months old) and old (18, 24, and 26 months old) male rats.…”

Section: Discussionmentioning

confidence: 99%

Age- and gender-related changes in glucose homeostasis in glucocorticoid-treated rats

Santos

Ferreira

Gonçalves-Neto

et al. 2014

Can. J. Physiol. Pharmacol.

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The disruption to glucose homeostasis upon glucocorticoid (GC) treatment in adult male rats has not been fully characterized in older rats or in females. Thus, we evaluated the age- and gender-related changes in glucose homeostasis in GC-treated rats. We injected male and female rats at 3 months and 12 months of age with either dexamethasone (1.0 mg/kg body mass, intraperitoneally) or saline, daily for 5 days. All of the GC-treated rats had decreased body mass and food intake, and adrenal hypotrophy. Increased glycemia was observed in all of the GC-treated groups and only the 3-month-old female rats were not glucose intolerant. Dexamethasone treatment resulted in hyperinsulinemia and hypertriacylglyceridemia in all of the GC-treated rats. The glucose-stimulated insulin secretion (GSIS) was higher in all of the dexamethasone-treated animals, but it was less pronounced in the older animals. The β-cell mass was increased in the younger male rats treated with dexamethasone. We conclude that dexamethasone treatment induces glucose intolerance in both the 3- and 12-month-old male rats as well as hyperinsulinemia and augmented GSIS. Three-month-old female rats are protected from glucose intolerance caused by GC, whereas 12-month-old female rats developed the same complications that were present in 3- and 12-month-old male rats.

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“…Since Sim1CreGRe3Δ mice become obese and have increased adiposity, this finding is suggestive of a difference in CORT function during early development compared to adulthood in mediating growth signaling. This ramification is supported by rat studies showing that prenatal dexamethasone application causes low birth weight (Drake et al, 2010), but dexamethasone application into adult rats causes an increase in enzymes responsible for synthesis of lipids, and thus increased visceral adiposity (Chimin et al, 2014). However evidence in most studies demonstrates catabolic effects of dexamethasone in adult rodents that lead to weight loss (Franco-Colín et al, 2006; Minet-Quinard et al, n.d.; Savary et al, 1998).…”

Section: Gr Disruption In the Hypothalamusmentioning

confidence: 97%

Dissection of glucocorticoid receptor-mediated inhibition of the hypothalamic–pituitary–adrenal axis by gene targeting in mice

Laryea

Muglia

Arnett

et al. 2015

Frontiers in Neuroendocrinology

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Negative feedback regulation of glucocorticoid (GC) synthesis and secretion occurs through the function of glucocorticoid receptor (GR) at sites in the hypothalamic-pituitary-adrenal (HPA) axis, as well as in brain regions such as the hippocampus, prefrontal cortex, and sympathetic nervous system. This function of GRs in negative feedback coordinates basal glucocorticoid secretion and stress-induced increases in secretion that integrate GC production with the magnitude and duration of the stressor. This review describes the effects of GR loss along major sites of negative feedback including the entire brain, the paraventricular nucleus of the hypothalamus (PVN), and the pituitary. In genetic mouse models, we evaluate circadian regulation of the HPA axis, stress-stimulated neuroendocrine response and behavioral activity, as well as the integrated response of organism metabolism. Our analysis provides information on contributions of region-specific GR-mediated negative feedback to provide insight in understanding HPA axis dysregulation and the pathogenesis of psychiatric and metabolic disorders.

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Chronic glucocorticoid treatment enhances lipogenic activity in visceral adipocytes of male Wistar rats

Abstract: The adaptations promoted by GC treatment in adipose metabolism seemed to be mainly due to the increased activity of enzymes that supply the NADPH required for lipogenesis than to the increase in enzymes that more directly deal with fatty acid synthesis itself.

Cited by 44 publications

References 37 publications

Brown adipose tissue remodelling induced by corticosterone in male Wistar rats

Brown adipose tissue remodelling induced by corticosterone in male Wistar rats

Age- and gender-related changes in glucose homeostasis in glucocorticoid-treated rats

Dissection of glucocorticoid receptor-mediated inhibition of the hypothalamic–pituitary–adrenal axis by gene targeting in mice

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