Table 1.
Metabolic responses to chronic activation of PPARα with FB in PPARα-/- mice.
Table 2.
Metabolic responses to chronic activation of PPARα with FB in FGF21-/- mice.
Fig 1.
Effects of FB on hepatic TG content and the lipogenic pathway in PPARα+/+ and PPARα-/- mice.
Fenofibrate (+ FB) was administered to PPARα+/+ and PPARα-/- mice on the background of C57BL/6N at a dose (50 mg/kg/day) for 3 weeks. (A) Effects on triglyceride (TG) content. (B) Representative images and (C) Quantification of Western blots for ACOX1 (peroxisomal acyl-CoA oxidase 1, PPARα activation marker) and lipogenic proteins: mSREBP1c (matured form of sterol regulatory element-binding protein 1 c), ACC (acetyl-CoA carboxylase), FAS (fatty acid synthase) and SCD1 (stearoyl-CoA desaturase 1). ** p<0.01 vs. control (-FB); n.s. not statistically significant. n = 5–6/group.
Fig 2.
Effects of FB on hepatic autophagic proteins in PPARα+/+ and PARα-/- mice.
Experiments were conducted as described in Fig 1. (A) Representative of images and (B) quantification of the Western blots for key autophagic proteins. Atg3 (autophagy-related gene protein 3), Atg4B (autophagy-related gene protein 4B), Atg5 (autophagy-related gene protein 5), Atg7 (autophagy-related gene protein 7), LC3 (microtubule-associated protein light chain 3) and p62 (polyubiquitin-binding protein p62). * p<0.05, ** p<0.01 vs control (-FB); † p<0.05, †† p<0.01 vs untreated PPARα+/+ mice; n.s. not statistically significant. n = 5–6/group.
Fig 3.
Effects of FB on hepatic TG content and lipogenic proteins in FGF21+/+ and FGF21-/- mice.
(A) Plasma levels of FGF21 in response to fasting. For B and C, FB was administered to FGF21+/+ and FGF21-/- mice on the background of C57BL/6J at a dose (50 mg/kg/day) for 3 weeks. (B) Liver TG content. (C) Representative images and quantification of the Western blots for ACOX1, mSREBP1c, ACC, FAS and SCD1. * p<0.05, ** p<0.01 vs control (-FB); n.s. not statistically significant, n = 5–6/group.
Fig 4.
Effects of FB on the content of autophagic proteins in the liver of FGF21+/+ and FGF21-/- mice.
FGF21+/+ and FGF21-/- mice were administrated with FB for 3 weeks as described in the methods. The liver samples were collected for Western blots for autophagic proteins including Atg3, Atg4B, Atg5, Atg7, Beclin-1, LC3 and p62. * p<0.05; ** p<0.01 vs group (- FB), n = 5–6/group.
Fig 5.
Effects of FB on the autophagy upstream pathways in PPARα+/+ and PARα-/- mice.
Liver samples were collected after 3 weeks of FB administration for Western blotting. (A) Effects of FB on key proteins of the mTOR pathway: mTOR (mammalian target of rapamycin), S6K (P70S6 serine/threonine kinase), 4EBP1 (eukaryotic translation initiation factor 4E-biniding protein). (B) Effects of FB on key proteins the insulin signaling pathway: Akt (protein kinase B) and GSK3β (glycogen synthase kinase 3 β). * p<0.05, ** p<0.01 control (-FB); n.s. not statistically significant, n = 5–6/group.
Fig 6.
Effects of FB on FoxO1 and SIRT1 in PPARα+/+ and PARα-/- mice.
Liver samples were collected after 3 weeks of FB administration. (A) Effects on the content, phosphorylation and acetylation (Ac) of FoxO1 the protein level. (B) Effects on the level of mRNA of FoxO1. (C) Effects on deacetylases, SIRT1 (silent mating type information regulation 2 homolog or NAD-dependent deacetylase sirtuin-1) and HDAC4 (histone deacetylases 4). * p<0.05, ** p<0.01 vs control (-FB); n.s. not statistically significant; n = 5–6/group.