Abstract
BackgroundThe role of cortisol and its increased action/availability is implicated in the pathogenesis of insulin resistance associated with obesity and metabolic syndrome but the mechanism of increased action/availability is not known. Availability of several other lipophilic hormones, drugs and pollutants are also reported to be increased in obesity. Increased lipids in the circulation are reported to alter the fluidity and permeability of membranes. Hyperlipidemia is also reported to alter the pharmacokinetics and pharmacodynamics of lipophilic molecules and also membrane fluidity and permeability. In this context we assumed that the hyperlipidemia associated with human obesity might play a role in the altered action/availability of cortisol and this in turn might have initiated the metabolic complications. To evaluate our assumption we have administered dexamethasone [low [50 μg/kg/day] or high [250 μg/kg/day] dose] to high-fat [coconut oil & vanaspati] fed rats and the results were compared with rats administered with either dexamethasone or high-fat.Results and DiscussionWithin two weeks, the rats co-administered with high-fat and dexamethasone developed severe hyperglycemia, hyperlipidemia and insulin resistance compared to rats treated either of them alone. High-fat fed rats treated with higher dose of dexamethasone were presented with severe hyperglycemia, insulin resistance and also severe glycosuria. The hyperlipidemia caused by high-fat feeding might have altered the transport and distribution of dexamethasone, probably by altering the physical state of membranes and transport proteins.ConclusionFrom the results obtained, it can be speculated that the altered lipid and cortisol metabolism could affect one another, forming a vicious cycle.
Highlights
The role of cortisol and its increased action/availability is implicated in the pathogenesis of insulin resistance associated with obesity and metabolic syndrome but the mechanism of increased action/availability is not known
Administration of Dex [both low and high dose] to highfat fed rats [High-fat treated (HF)-High-dose Dex (HD) and High-fat + Low-dose of Dex (HF-Low-dose of Dex (LD))] have caused severe hyperglycemia, hyperinsulinemia, altered lipid profile, reduced food intake, decreased insulinogenic index and Glucose infusion rate (GIR) compared to the corresponding Dex [HD and LD] or high-fat
Our results shows that the hyperglycemic effect of Dex have been potentiated/aggravated when it was administered to high-fat fed [High-fat + High-dose of Dex (HF-HD) and HF-LD] rats compared to Dex alone [HD or LD] treated rats
Summary
The role of cortisol and its increased action/availability is implicated in the pathogenesis of insulin resistance associated with obesity and metabolic syndrome but the mechanism of increased action/availability is not known. Hyperlipidemia is reported to alter the pharmacokinetics and pharmacodynamics of lipophilic molecules and membrane fluidity and permeability. In this context we assumed that the hyperlipidemia associated with human obesity might play a role in the altered action/availability of cortisol and this in turn might have initiated the metabolic complications. Type 2 diabetes, obesity and metabolic syndrome are emerging at an alarming rate worldwide [1,2,3]. Understanding the biology of these systems will inform the search for interventions that prevent or treat insulin resistance and its associated pathologies [12]
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