Multiple effects of a short-term dexamethasone treatment in human skeletal muscle and adipose tissue

Abstract

Glucocorticoids are frequently prescribed drugs with important side-effects such as glucose intolerance and tissue remodeling. The goal was to explore the molecular basis of the response of skeletal muscle and adipose tissue during a short-term dexamethasone treatment to better understand the induction of side-effects of glucocorticoids on these metabolic tissues. Fifteen healthy male subjects were assigned to a 4-day treatment with dexamethasone at 4 mg/day. The primary outcome measures were changes in gene expression profiling of subcutaneous skeletal muscle and adipose tissue. Urinary cortisol, plasma, and metabolic biochemistry were also assessed. In both tissues the prominent observation was a response to stress and increased inflammatory responses. An upregulation of the serum amyloid A was detected in skeletal muscle, adipose tissue, and plasma, whereas circulating levels of C reactive protein, another acute phase protein, decreased along with a worsened insulin sensitivity index. As tissue-specific features, tissue remodeling was shown in skeletal muscle while the adipose tissue exhibited a decreased energy metabolism. Several limitations might be raised due to the small number of subjects investigated: a possible cross talk with the mineralocorticoid receptor, and a single time point may not identify regulations occurring during longitudinal treatment. In line with the known physiological effect of glucocorticoids the early modulation of stress response genes was observed. An unexpected feature was the upregulation of the inflammatory and immune pathways. The identification of novel impact on two glucocorticoid target tissues provides a molecular basis for the design of more specific glucocorticoids devoid of adverse effects.

Anti-Inflammatory Potential of Monogalactosyl Diacylglycerols and a Monoacylglycerol from the Edible Brown Seaweed Fucus spiralis Linnaeus

“…Glucocorticoids are commonly prescribed for the treatment of several situations of inflammatory disorders; nevertheless, there are plenty of undesirable side effects associated with both acute and long term treatments [29]. For this reason, we believe that glycerolipids and MGDGs may constitute an alternative to common anti-inflammatory drugs, as they present a good therapeutic activity without known side effects.…”

Improvement of spinal non-viral IL-10gene delivery by D-mannose as a transgene adjuvant to control chronic neuropathic pain

“…Further evidence that dexamethasone can play a role in cell migration was demonstrated by its effects on augmenting the actions of the chemokine receptor, CXCR4 on T cells [74]. A recent study conducted in healthy males revealed elevated inflammatory responses in skeletal and adipose tissue following acute dexamethasone treatment [75]. Given strong evidence exists that peripheral neuropathy in rodent models leads to a weakened blood-spinal barrier with robust chemokine/proinflammatory cytokine signaling and infiltration of activated macrophages [10], it is possible that acute i.t.…”

A genome-wide signature of glucocorticoid receptor binding in neuronal PC12 cells

“…GR is an important transcription factor in neurons and is known to exert effects on neuronal structure and plasticity. So far the focus on GR-mediated action of glucocorticoids in a neuronal context has remained largely in the dark and most of the knowledge on GR modes of action, GR responsive genes and pathways and crosstalk partners of GR has come from studies on peripheral tissues including the immune system, the respiratory tract, skeletal muscle and adipose tissue as well as various types of cancer cells [40-42]. Approximately 1,100 genomic binding sites of GR were identified in neuronal PC12 cells, the majority of which are novel and display only very limited overlap with GR binding sites in other non-neuronal cell types.…”