MECHANISMS IN ENDOCRINOLOGY: Local and systemic effects of glucocorticoids on metabolism: new lessons from animal models

Abstract

Glucocorticoids regulate a remarkable variety of essential functions, including development, immunomodulation, maintenance of circadian rhythm and the response to stress. Glucocorticoids acutely increase energy availability; this is accomplished not only by mobilizing energy stores, but also by diverting energy away from anabolic processes in tissues such as skeletal muscle and bone. While this metabolic shift is advantageous in the short term, prolonged glucocorticoid exposure frequently results in central obesity, insulin resistance, hyperglycaemia, dyslipidaemia, muscle wasting and osteoporosis. Understanding how glucocorticoids affect nutrient partitioning is therefore critical for preventing the side effects of glucocorticoid treatment. Independently of circulating glucocorticoids, intracellular glucocorticoid activity is regulated by the 11β-hydroxysteroid dehydrogenases 1 and 2 (11β-HSD1 and 2), which activate and inactivate glucocorticoids, respectively. Excessive 11β-HSD1 activity, amplifying local glucocorticoid activity in tissues such as adipose tissue and bone may contribute to visceral obesity, insulin resistance and aging-related bone loss in humans. Several recent findings in animals have considerably expanded our understanding of how glucocorticoids exert their dysmetabolic effects. In mice, disrupting glucocorticoid signalling in either adipose tissue or bone produces marked effects on energy homeostasis. Glucocorticoids have also been shown to influence brown adipose tissue thermogenesis (acute activation, chronic suppression), in both rodents and humans. Lastly, recent studies in mice have demonstrated that many dysmetabolic effects of glucocorticoids are sexually dimorphic, although corresponding results in humans are lacking. Together, these studies have illuminated the mechanisms by which glucocorticoids exert their metabolic effects; and have guided us towards more targeted future treatments for metabolic diseases.

Endogenous Retroviruses Augment Amphibian (Xenopus laevis) Tadpole Antiviral Protection

“…Corticosteroid hormones (CHs) are critical to transitioning amphibian tadpoles into metamorphosis (23), while FV3 encodes a b-hydroxysteroid dehydrogenase homolog (52L), which is thought to be important to viral immune evasion (24). Hydroxysteroid dehydrogenase enzymes are typically involved in steroid biosynthesis and metabolism (25). Because our findings indicated antiviral protection of tadpole kidneys decreased with onset of metamorphosis, we reasoned that the FV3 52L confers evasion of host immunity by promoting metamorphosis.…”

Dexamethasone-Induced Adipose Tissue Redistribution and Metabolic Changes: Is Gene Expression the Main Factor? An Animal Model of Chronic Hypercortisolism

“…All protocols described were approved by the Committee of Ethics in the Use of Animals of the Institute of Biomedical Sciences, University of Sao Paulo (CEUA-ICB/USP #89/2016; #26/2017; 9535190219). For the experiments, SPF-certified 8 weeks old male Wistar Hannover rats obtained from the Institute of Biomedical Sciences Animal Facility were used, since sex could be an important variable in adipose tissue analyzes [ 36 ]. Each rat was housed in an individual open polycarbonate cage (model 1291H, 425 × 266 × 185 mm and 800 cm 2 of floor area, Tecniplast ® , Buguggiate, VA, Itália Italy) in our laboratory private room at Animal Care of the Department of Physiology and Biophysics for 4 weeks of acclimatization to the new space, light cycle, and human–rat bond before the treatment protocol starts.…”

Glucose and lipid metabolism abnormalities in Cushing's syndrome

“…27 Further study showed an acute (36-hour) GC exposure in male human subjects increases UCP1 protein levels and brown adipose tissue thermogenic activity, whereas chronic GC exposure (at least two weeks) decreases brown adipose tissue activation. 28,29 Mice treated with corticosterone for four weeks showed marked lipid accumulation in brown adipose tissue and an 8% decrease in UCP1 protein expression. 30…”