Glucocorticoids inhibit mitochondrial matrix acyl-CoA dehydrogenases and fatty acid beta-oxidation

The American Journal of Physiology
P LetteronD Pessayre

Abstract

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.

Citations

Sep 7, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Michelino Di Rosa, Lucia Malaguarnera
Aug 2, 2007·American Journal of Physiology. Endocrinology and Metabolism·Magalie BerthiaumeYves Deshaies
Oct 12, 2013·American Journal of Physiology. Gastrointestinal and Liver Physiology·Xiuhua SunZhanxiang Zhou
Aug 15, 2015·BioMed Research International·Liane Rabinowich, Oren Shibolet
May 6, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Leili RahimiFaramarz Ismail-Beigi
Aug 26, 2004·American Journal of Physiology. Endocrinology and Metabolism·M Korach-AndréD Laurent
Nov 8, 2018·BioMed Research International·Rosa María MateosAlfonso M Lechuga-Sancho
Nov 2, 2019·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Chantal A VellaLorraine P Turcotte
Jul 14, 2021·Expert Opinion on Drug Safety·Miren García-CortésRaúl J Andrade

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