AIMS: Glucocorticoids, such as dexamethasone, enhance hepatic energy metabolism 
and gluconeogenesis partly through changes in mitochondrial function. 
Mitochondrial function is influenced by the balance between mitochondrial fusion 
and fission events. However, whether glucocorticoids modulate mitochondrial 
function through the regulation of mitochondrial dynamics is currently unknown.
RESULTS: Here, we report that the effects of dexamethasone on mitochondrial 
function and gluconeogenesis in hepatoma cells are dependent on the 
mitochondrial fission protein dynamin-related protein 1 (Drp1). Dexamethasone 
increased routine oxygen consumption, maximal respiratory capacity, superoxide 
anion, proton leak, and gluconeogenesis in hepatoma cells. Under these 
conditions, dexamethasone altered mitochondrial morphology, which was paralleled 
by a large increase in Drp1 expression, and reduced mitofusin 1 (Mfn1) and Mfn2. 
In vivo dexamethasone treatment also enhanced Drp1 expression in mouse liver. On 
the basis of these observations, we analyzed the dependence on the Drp1 function 
of dexamethasone effects on mitochondrial respiration and gluconeogenesis. We 
show that the increase in mitochondrial respiration and gluconeogenesis induced 
by dexamethasone are hampered by the inhibition of Drp1 function.
INNOVATION: Our findings provide the first evidence that the effects of 
glucocorticoids on hepatic metabolism require the mitochondrial fission protein 
Drp1.
CONCLUSION: In summary, we demonstrate that the mitochondrial effects of 
dexamethasone both on mitochondrial respiration and on the gluconeogenic pathway 
depend on Drp1.