Alterations in downstream protein expression pointed to significant activation of transforming growth factor β, SMAD family member 3, β-catenin, Nrf2, SREBP-LXRα and nuclear receptor-interacting protein 1 (NRIP1), and inhibition of PPARs and p53 in human NASH biopsies and/or HCCs, suggesting their involvement in accumulation of lipids, development of fibrosis, oxidative stress, cell proliferation and suppression of apoptosis in NASH hepatocarcinogenesis.
Amelioration by chicory seed extract of diabetes- and oleic acid-induced non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) via modulation of PPARα and SREBP-1.
We used real-time polymerase chain reaction (RT-PCR) analysis to evaluate the hepatic and intestinal expression level of all genes studied (TLR2, TLR4, TLR9, LXRα, SREBP1C, ACC1, FAS, PPARα, CPT1α, CROT, SREBP2, ABCA1, ABCG1 and FXR in the liver; TLR2, TLR4, TLR5, TLR9, GLP-1R, DPP-4, FXR and PPARɣ in the jejunum) in 82 women with MO with normal liver histology (NL, n = 29), SS (n = 32), and NASH (n = 21).
The efficacy of peroxisome proliferator-activated receptor α-agonists (e.g., fibrates) against nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in humans is not known.
The absence of an approved therapeutic agent for NASH is the reason for investigating saroglitazar (SAR) which showed promising effects as a dual PPAR-α/γ agonist in recent studies on NASH.
Silibinin can ameliorate some metabolic alterations and induce some molecular changes by activating the CFLAR-JNK pathway and thereby regulating its downstream target genes involved in lipid metabolism (PPARα, SREBP-1C and PNPLA3), glucose uptake (PI3K-AKT), oxidative stress (NRF2, CYP2E1, CYP4A) and inflammatory response(NO) in OA-treated HepG2 cells demonstrating its possible use in ameliorating various symptoms of NASH.
We established a mouse model of developmental nonalcoholic steatohepatitis (NASH) by feeding a high polyunsaturated fat liquid diet to female glutathione-S-transferase 4-4 (Gsta4<sup>-/-</sup>)/peroxisome proliferator activated receptor α (Ppara<sup>-/-</sup>) double knockout 129/SvJ mice for 12 weeks from weaning.
Liver PPARα expression negatively correlated with the presence of NASH (p=0.001) and with severity of steatosis (p=0.003), ballooning (p=0.001), NASH activity score (p=0.008) and fibrosis (p=0.003).
In a complementary fast food (FF) diet NASH model, mimicking features of the metabolic syndrome, miR-21 levels increase in both liver and muscle, concomitantly with decreased expression of peroxisome proliferator-activated receptor α (PPARα), a key miR-21 target.
In vivo studies showed that MP treatment activated PPARα expression, that in turns, promoted β-oxidation protein and gene expressions, suppressed TNFα, MCP1, TGFβ1 and Colla1 protein and gene expression levels, contributing to the prevention of NASH.
Hepatic miR-141 and miR-200c RNA levels were highly induced in human patients with NASH fatty liver and in WT MCD mice. miR-141/200c-/- MCD mice had reduced liver weights and triglyceride (TG) levels, which was associated with increased microsomal TG transfer protein (MTTP) and PPARα but reduced SREBP1c and FAS expression.
Therefore, this study for the first time explored the preventive effect of trans-chalcone on NASH through the modulation of sterol regulatory element binding protein (SREBP)-1c, SREBP-2, hepatic fatty acid synthesis (FAS) enzyme, proliferator-activated receptor (PPAR)-α, and PPAR-γ2 levels, which are involved in hepatic lipid metabolism.
Osthole, a coumarin derivative, can increase hepatic peroxisome proliferator-activated receptor α (PPARα) expression and reduce hepatic steatosis and inflammatory response in rats with non-alcoholic steatohepatitis (NASH).