title: Epinephrine deficiency results in intact glucose counter-regulation, severe hepatic steatosis and possible defective autophagy in fasting mice.
abstract: Epinephrine is one of the major hormones involved in glucose counter-regulation and gluconeogenesis. However, little is known about its importance in energy homeostasis during fasting. Our objective is to study the specific role of epinephrine in glucose and lipid metabolism during starvation. In our experiment, we subject regular mice and epinephrine-deficient mice to a 48-h fast then we evaluate the different metabolic responses to fasting. Our results show that epinephrine is not required for glucose counter-regulation: epinephrine-deficient mice maintain their blood glucose at normal fasting levels via glycogenolysis and gluconeogenesis, with normal fasting-induced changes in the peroxisomal activators: peroxisome proliferator activated receptor γ coactivator α (PGC-1α), fibroblast growth factor 21 (FGF-21), peroxisome proliferator activated receptor α (PPAR-α), and sterol regulatory element binding protein (SREBP-1c). However, fasted epinephrine-deficient mice develop severe ketosis and hepatic steatosis, with evidence for inhibition of hepatic autophagy, a process that normally provides essential energy via degradation of hepatic triglycerides during starvation. We conclude that, during fasting, epinephrine is not required for glucose homeostasis, lipolysis or ketogenesis. Epinephrine may have an essential role in lipid handling, possibly via an autophagy-dependent mechanism.
authors.affiliation: Division of Critical Care Medicine, Department of Anesthesiology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA. rsharara@aub.edu.lb
authors.forename: Rana I
authors.initials: RI
authors.lastname: Sharara-Chami
authors.forename: Yingjiang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Steven
authors.initials: S
authors.lastname: Ebert
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.forename: Umut
authors.initials: U
authors.lastname: Ozcan
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Majzoub
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D001343:Autophagy; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D017931:DNA Primers; D004837:Epinephrine / Q000494:pharmacology*; D005215:Fasting; D005234:Fatty Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; D017931:DNA Primers; D008112:Liver Glycogen; D004837:Epinephrine