Fat feeding potentiates the diabetogenic effect of dexamethasone in Wistar rats.

Background: 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. 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 mug/kg/day] or high [250 mug/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 Discussion: Within 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.

Conclusion: From the results obtained, it can be speculated that the altered lipid and cortisol metabolism could affect one another, forming a vicious cycle.