Session: OR45-HPA Axis
Room 135 (Moscone Center)
We investigated the role of ACTH and glucocorticoids on BAT and WAT in 4 models: cold-exposed mice; mouse brown adipocyte T37i cells; primary cultured murine BAT and inguinal WAT cells; and 18F-deoxyglucose (18F-FDG) positron emission tomography (PET) scans of ACTH-injected mice. In the cold-exposed mice we measured plasma ACTH and 24h fecal corticosterone levels and analyzed interscapular BAT and inguinal WAT. To study a direct effect of the HPA-hormones on BAT and WAT, we treated adipocytes with ACTH and dexamethasone. To test the direct effects of ACTH in vivo, we performed micro 18F-FDG-PET-scans.
Twenty-four hours of cold exposure resulted in: a 3.1-fold increase in Ucp1 mRNA expression in BAT (p=0.002); a 4-fold decrease in BAT lipid content (p=0.001); and increased intensity of UCP1 immunostaining. Browning of inguinal WAT was confirmed by a 20-fold increase in Ucp1 mRNA expression (p=0.002), and increased UCP1 immunostaining. Cold exposure also enhanced the HPA-axis as serum ACTH (597 ± 112.8 vs 1203.7 ± 158.4 pg/mL, p= 0.03) and fecal corticosterone (117.7± 5.9 vs 219.9 ±16.7 ng/24h, p=0.008) excretion doubled. In T37i cells, the glucocorticoid receptor agonist dexamethasone slightly suppressed Ucp1, whereas ACTH dose dependently induced Ucp1 expression and markedly increased glycerol release (p=0.03), indicative for enhanced lipolysis. In addition, ACTH elevated Ucp1 expression in cultured BAT (3-fold, p= 0.03) and inguinal WAT (3.7-fold, p=0.01) primary cells. Finally, a single ACTH bolus doubled 18F-FDG uptake by interscapular BAT of mice (p=0.02).
In conclusion, our results suggest that ACTH can directly activate brown adipocytes and promote browning of inguinal WAT in mice. Stimulation of the HPA axis upon cold exposure may therefore play an important role in the induction of BAT activity and browning of WAT.
Nothing to Disclose: JCV, AG, CQ, JS, ML, PJD, RM, UP, AJV, APT
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