IRF8 regulates hepatic lipid metabolism via the BMAL1/PPARγ axis. (IMAGE)
Caption
(A) HEK293T cells co-transfected with Pparγ promoter reporter (pGL3-Pparγ), either pCDNA3.1 or BAML1 overexpression plasmid, were analyzed for relative luciferase activity (FLUC/RLUC) (n = 3 biologically independent samples). (B–G) Protein levels (n = 3 biologically independent mice from two groups) and relative mRNA levels of Pparγ and its target genes were assessed in the livers from (B, C) C57BL/6J male mice treated with AAV-IRF8 or AAV-GFP fed on CD (n = 6 biologically independent mice from two groups), and (D, E) C57BL/6J male mice treated with AAV-IRF8 or AAV-GFP fed on HFD (n = 8 biologically independent mice from two groups), and (F, G) C57BL/6J mice treated with AAV-shIRF8 or AAV-GFP fed on HFD. (H, I) Protein levels (H) and relative mRNA expression (I) of Pparγ and its target genes (n = 5 biologically independent mice from two groups) were analyzed in MPHs after transfection with combinations of Ad-GFP + si-NC, Ad-IRF8 + si-NC, Ad-GFP + si-BMAL1, and Ad-IRF8 + si-BMAL1, in the presence of 0.1 mM palmitic acid (PA) treatment (n = 3 biologically independent samples). (J, K) Protein levels (J) and relative mRNA expression (K) of Pparγ and its target genes were determined in MPHs transfected with si-NC + Vector, si-IRF8 + Vector, si-NC + BMAL1 OE, and si-IRF8 + BMAL1 OE, concurrently with 0.1 mM PA treatment (n = 3 biologically independent samples). Data are presented as mean ± standard error of the mean. p values were calculated using an unpaired two-tailed Student's t-test (B, D, F, H, I, J). IRF8, interferon regulatory factor 8; BMAL1, brain and muscle ARNT-like 1; PPARγ, peroxisome proliferator-activated receptor γ; HFD, high-fat diet; CD, chow diet; AAV, adeno-associated virus; GFP, green fluorescent protein; MPHs, mouse primary hepatocytes.
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Genes & Diseases
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