ECB-ART-52112
Biomedicines
2022 Sep 19;109:. doi: 10.3390/biomedicines10092328.
Show Gene links
Show Anatomy links
Dexamethasone-Induced Adipose Tissue Redistribution and Metabolic Changes: Is Gene Expression the Main Factor? An Animal Model of Chronic Hypercortisolism.
de Fatima Silva F
,
Komino ACM
,
Andreotti S
,
Boltes Reis G
,
Caminhotto RO
,
Landgraf RG
,
de Souza GO
,
Sertié RAL
,
Collins S
,
Donato J
,
Bessa Lima F
.
???displayArticle.abstract???
Chronic hypercortisolism has been associated with the development of several metabolic alterations, mostly caused by the effects of chronic glucocorticoid (GC) exposure over gene expression. The metabolic changes can be partially explained by the GC actions on different adipose tissues (ATs), leading to central obesity. In this regard, we aimed to characterize an experimental model of iatrogenic hypercortisolism in rats with significant AT redistribution. Male Wistar rats were distributed into control (CT) and GC-treated, which received dexamethasone sodium phosphate (0.5 mg/kg/day) by an osmotic minipump, for 4 weeks. GC-treated rats reproduced several characteristics observed in human hypercortisolism/Cushing's syndrome, such as HPA axis inhibition, glucose intolerance, insulin resistance, dyslipidemia, hepatic lipid accumulation, and AT redistribution. There was an increase in the mesenteric (meWAT), perirenal (prWAT), and interscapular brown (BAT) ATs mass, but a reduction of the retroperitoneal (rpWAT) mass compared to CT rats. Overexpressed lipolytic and lipogenic gene profiles were observed in white adipose tissue (WAT) of GC rats as BAT dysfunction and whitening. The AT remodeling in response to GC excess showed more importance than the increase of AT mass per se, and it cannot be explained just by GC regulation of gene transcription.
???displayArticle.pubmedLink??? 36140428
???displayArticle.link??? Biomedicines
???displayArticle.grants??? [+]
2016/25129-4, 2018/11145-3, and 2018/16856-5. São Paulo Research Foundation
References [+] :
Ahmed,
Dexamethasone for the Treatment of Coronavirus Disease (COVID-19): a Review.
2020, Pubmed
Ahmed, Dexamethasone for the Treatment of Coronavirus Disease (COVID-19): a Review. 2020, Pubmed
Alev, Glucocorticoid-Induced Changes in Rat Skeletal Muscle Biomechanical and Viscoelastic Properties: Aspects of Aging. 2018, Pubmed
Andersson, Changes in subcutaneous fat cell volume and insulin sensitivity after weight loss. 2014, Pubmed
Arnaldi, Pathophysiology of dyslipidemia in Cushing's syndrome. 2010, Pubmed
Bahceci, The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6 and high sensitivity C-reactive protein levels. Is adipocyte size associated with inflammation in adults? 2007, Pubmed
Batista, Heterogeneous time-dependent response of adipose tissue during the development of cancer cachexia. 2012, Pubmed
Beaupere, Molecular Mechanisms of Glucocorticoid-Induced Insulin Resistance. 2021, Pubmed
Bel, Chronic glucocorticoid exposure causes brown adipose tissue whitening, alters whole-body glucose metabolism and increases tissue uncoupling protein-1. 2022, Pubmed
Berbée, Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development. 2015, Pubmed
Bowles, A peripheral endocannabinoid mechanism contributes to glucocorticoid-mediated metabolic syndrome. 2015, Pubmed
Buttgereit, Novel glucocorticoids: where are we now and where do we want to go? 2015, Pubmed
Campbell, Adipogenic and lipolytic effects of chronic glucocorticoid exposure. 2011, Pubmed
Cannon, The biochemistry of an inefficient tissue: brown adipose tissue. 1985, Pubmed
Caprio, Pivotal role of the mineralocorticoid receptor in corticosteroid-induced adipogenesis. 2007, Pubmed
Chanson, Metabolic syndrome in Cushing's syndrome. 2010, Pubmed
Chatterjee, An epidemic of iatrogenic Cushing's syndrome in anticipation in post-COVID era. 2022, Pubmed
Chimin, Chronic glucocorticoid treatment enhances lipogenic activity in visceral adipocytes of male Wistar rats. 2014, Pubmed
Choe, Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders. 2016, Pubmed
Christ-Crain, AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome. 2008, Pubmed
Chusyd, Relationships between Rodent White Adipose Fat Pads and Human White Adipose Fat Depots. 2016, Pubmed
Clark, Anti-inflammatory functions of glucocorticoid-induced genes. 2007, Pubmed
Coleman, Enzymes of triacylglycerol synthesis and their regulation. 2004, Pubmed
Considine, Serum immunoreactive-leptin concentrations in normal-weight and obese humans. 1996, Pubmed
Di Girolamo, A simple method to determine fat cell size and number in four mammalian species. 1971, Pubmed
Dimitriadis, Insulin effects in muscle and adipose tissue. 2011, Pubmed
Dolinsky, Regulation of the enzymes of hepatic microsomal triacylglycerol lipolysis and re-esterification by the glucocorticoid dexamethasone. 2004, Pubmed
FOLCH, A simple method for the isolation and purification of total lipides from animal tissues. 1957, Pubmed
Fadel, Early Short-Course Corticosteroids in Hospitalized Patients With COVID-19. 2020, Pubmed
Feelders, The burden of Cushing's disease: clinical and health-related quality of life aspects. 2012, Pubmed
Ferraù, Metabolic comorbidities in Cushing's syndrome. 2015, Pubmed
Ferreira, Differential regulation of glyceroneogenesis by glucocorticoids in epididymal and retroperitoneal white adipose tissue from rats. 2017, Pubmed
Fox, Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. 2007, Pubmed
Friedewald, Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. 1972, Pubmed
Halvorsen, Thiazolidinediones and glucocorticoids synergistically induce differentiation of human adipose tissue stromal cells: biochemical, cellular, and molecular analysis. 2001, Pubmed
He, Structures and mechanism for the design of highly potent glucocorticoids. 2014, Pubmed
Heitzer, Glucocorticoid receptor physiology. 2007, Pubmed
Hill, Insights into an adipocyte whitening program. 2015, Pubmed
Hoffstedt, Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity. 2010, Pubmed
Kadmiel, Glucocorticoid receptor signaling in health and disease. 2013, Pubmed
Kobayashi, Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance. 2011, Pubmed
Lafontan, Advances in adipose tissue metabolism. 2008, Pubmed
Lecoq, Genomic and non-genomic effects of dexamethasone on equine peripheral blood neutrophils. 2009, Pubmed
Lee, Hormonal Regulation of Adipogenesis. 2017, Pubmed
Lee, Body fat distribution is more predictive of all-cause mortality than overall adiposity. 2018, Pubmed
Lee, Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity. 2014, Pubmed
Lester, The use of dexamethasone in the treatment of COVID-19. 2020, Pubmed
Liu, A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. 2013, Pubmed
Liu, Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81. 2009, Pubmed
Lynes, Deciphering adipose tissue heterogeneity. 2018, Pubmed
Macfarlane, Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome. 2008, Pubmed
McNeill, Substrate Utilization by Brown Adipose Tissue: What's Hot and What's Not? 2020, Pubmed
Minetto, Quantitative and qualitative adaptations of muscle fibers to glucocorticoids. 2015, Pubmed
Mir, Genomic and Non-Genomic Actions of Glucocorticoids on Adipose Tissue Lipid Metabolism. 2021, Pubmed
Mitsugi, Simultaneous determination of blood levels of corticosterone and growth hormone in the male rat: relation to sleep-wakefulness cycle. 1985, Pubmed
Mousovich-Neto, Brown adipose tissue remodelling induced by corticosterone in male Wistar rats. 2019, Pubmed
Murano, Noradrenergic parenchymal nerve fiber branching after cold acclimatisation correlates with brown adipocyte density in mouse adipose organ. 2009, Pubmed
Newsholme, Integration of biochemical and physiologic effects of insulin on glucose metabolism. 2001, Pubmed
Nieman, Diagnosis of Cushing's Syndrome in the Modern Era. 2018, Pubmed
Nieman, Cushing's syndrome: update on signs, symptoms and biochemical screening. 2015, Pubmed
Nye, Reassessing triglyceride synthesis in adipose tissue. 2008, Pubmed
Nye, Glyceroneogenesis is the dominant pathway for triglyceride glycerol synthesis in vivo in the rat. 2008, Pubmed
Palmer, The sexual dimorphism of obesity. 2015, Pubmed
Paragliola, Treatment with Synthetic Glucocorticoids and the Hypothalamus-Pituitary-Adrenal Axis. 2017, Pubmed
Peckett, The effects of glucocorticoids on adipose tissue lipid metabolism. 2011, Pubmed
Pellegrinelli, Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. 2016, Pubmed
Petersen, MCT1 and MCT4 Expression and Lactate Flux Activity Increase During White and Brown Adipogenesis and Impact Adipocyte Metabolism. 2017, Pubmed
Pivonello, Cushing's disease: the burden of illness. 2017, Pubmed
Pleasure, Atrophy of skeletal muscle in patients with Cushing's syndrome. 1970, Pubmed
Poggioli, Dexamethasone reduces energy expenditure and increases susceptibility to diet-induced obesity in mice. 2013, Pubmed
Proença, New concepts in white adipose tissue physiology. 2014, Pubmed
RODBELL, METABOLISM OF ISOLATED FAT CELLS. I. EFFECTS OF HORMONES ON GLUCOSE METABOLISM AND LIPOLYSIS. 1964, Pubmed
Ramamoorthy, Corticosteroids: Mechanisms of Action in Health and Disease. 2016, Pubmed
Rebuffat, The 11-ketosteroid 11-ketodexamethasone is a glucocorticoid receptor agonist. 2004, Pubmed
Saggerson, Lipogenesis in rat brown adipocytes. Effects of insulin and noradrenaline, contributions from glucose and lactate as precursors and comparisons with white adipocytes. 1988, Pubmed
Sanchez-Gurmaches, Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis. 2018, Pubmed
Saponaro, The Subtle Balance between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis. 2015, Pubmed
Scaroni, Glucose Metabolism Abnormalities in Cushing Syndrome: From Molecular Basis to Clinical Management. 2017, Pubmed
Schoettl, Heterogeneity of adipose tissue in development and metabolic function. 2018, Pubmed
Schoneveld, Mechanisms of glucocorticoid signalling. 2004, Pubmed
Scotney, Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo. 2017, Pubmed
Sengupta, The Laboratory Rat: Relating Its Age With Human's. 2013, Pubmed
Sertie, The mechanisms involved in the increased adiposity induced by interruption of regular physical exercise practice. 2019, Pubmed
Sertié, Fat gain with physical detraining is correlated with increased glucose transport and oxidation in periepididymal white adipose tissue in rats. 2015, Pubmed
Shimizu, The Whitening of Brown Fat and Its Implications for Weight Management in Obesity. 2015, Pubmed
Skurk, Relationship between adipocyte size and adipokine expression and secretion. 2007, Pubmed
Smith, Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. 2001, Pubmed
Soumano, Glucocorticoids inhibit the transcriptional response of the uncoupling protein-1 gene to adrenergic stimulation in a brown adipose cell line. 2000, Pubmed
Swarbrick, MECHANISMS IN ENDOCRINOLOGY: Local and systemic effects of glucocorticoids on metabolism: new lessons from animal models. 2021, Pubmed
Velasco, Circadian rhythms of plasma corticosterone at different times after induction of diabetes. Responses to corticoadrenal stimulation in light and dark phases. 1993, Pubmed
Wallace, Use and abuse of HOMA modeling. 2004, Pubmed
Wu, Timing of glucocorticoid administration determines severity of lipid metabolism and behavioral effects in rats. 2017, Pubmed
Xu, Direct effect of glucocorticoids on lipolysis in adipocytes. 2009, Pubmed
Zhao, Hormonal regulation of acetyl-CoA carboxylase isoenzyme gene transcription. 2010, Pubmed
de Oliveira Caminhotto, Physiological concentrations of β-hydroxybutyrate do not promote adipocyte browning. 2019, Pubmed
van den Beukel, Cold Exposure Partially Corrects Disturbances in Lipid Metabolism in a Male Mouse Model of Glucocorticoid Excess. 2015, Pubmed