Glucocorticoids inhibit mitochondrial matrix acyl-CoA dehydrogenases and fatty acid beta-oxidation.
Glucocorticoid administration may produce fatty liver in humans. We investigated the effects of dexamethasone on hepatic mitochondria and lipid metabolism in mice. Dexamethasone 21-phosphate (20 microM) did not inhibit the mitochondrial inner membrane-bound very-long-chain acyl-CoA dehydrogenase but inhibited the matrixlocated long-, medium-, and short-chain dehydrogenases. Dexamethasone 21-phosphate (20 microM) inhibited the first beta-oxidation cycle of [1-(14C)]butyric acid and [1-(14C)]octanoic acid but not that of [1-(14C)]palmitic acid. Administration of dexamethasone 21-phosphate (100 mg/kg) decreased the in vivo oxidation of [1-(14C)]butyric acid and [1-(14C)]octanoic acid into [14C]CO2 but not that of [1-(14C)]palmitic acid and decreased the hepatic secretion of triglycerides. After 5 days of treatment (100 mg/kg daily), hepatic triglycerides were increased and both microvesicular steatosis and ultrastructural mitochondrial lesions were present. In conclusion, glucocorticoids inhibit medium- and short-chain acyl-CoA dehydrogenation and hepatic lipid secretion in mice. These effects may account for their steatogenic effects in humans.
Lettéron
P
P
Institut National de la Santé et de la Recherche Médicale U. 24, Clichy, France.
Brahimi-Bourouina
N
N
Robin
M A
MA
Moreau
A
A
Feldmann
G
G
Pessayre
D
D
D044944:Acyl-CoA Dehydrogenases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008930:Mitochondria, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D019308:Palmitic Acid / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism
D005227:Fatty Acids; D005938:Glucocorticoids; D013256:Steroids; D014280:Triglycerides; D019308:Palmitic Acid; D003907:Dexamethasone; D044944:Acyl-CoA Dehydrogenases