A novel specific peroxisome proliferator-activated receptor γ (PPARγ) modulator YR4-42 ameliorates hyperglycaemia and dyslipidaemia and hepatic steatosis in diet-induced obese mice.
These findings suggest that fatty acids treatment and the overfeeding can induce the up-regulation of CYP2C45 expression possibly via PPARγ and that the induction of PK and ALOX5 in goose fatty liver is at least partially attributed to fatty acid-induced expression of CYP2C45.
In addition, the interaction between FoxO1 and PPARγ was shown to induce hepatic steatosis in aging and db/db mice.We provide evidence that, in aged rats, FoxO1 interaction with PPARγ promotes hepatic steatosis, due to hyperglycemia-induced ER stress, which causes an impairment in Akt signaling, such in aging-related diabetes.
These findings indicate new mechanisms of action for both PPARα and PPARγ, and new potential treatment options for nonalcoholic fatty liver disease (NAFLD) and steatosis.This article has an associated First Person interview with the first author of the paper.
Based on our analysis, it is predicted that the disruption in the regulation of transcription factors such as AP-1, PPARγ, and NF-κB could contribute to the liver progression from cirrhosis to steatosis and eventually to HCC.
We speculated that the subcutaneously injected Phe was transferred to the liver through blood circulation, which may have induced the elevation of PPARγ directly or indirectly, leading to liver steatosis.
Taken together, these results indicated that KCCM attributed to KCs dysfunction facilitated hepatocyte steatosis through promoting expressing SOCS3; but PPARγ agonist ROZ alleviated steatosis through reducing SOCS3 expression by inhibiting JAK2/STAT3 in hepatocytes.
Hepatic PPARγ plays an opposing role in controlling steatosis and neutrophil infiltration, leading to dissociation between steatosis and inflammation; acute ethanol gavage attenuates hepatic PPARγ activation and subsequently up-regulates hepatic CXCL1/interleukin-8 expression, thereby exacerbating hepatic neutrophil infiltration.(Hepatology 2017;66:108-123).
These results, coupled with previous reports, suggest that Cd36-mediated FA uptake and MAG pathway-mediated FA esterification are major targets of hepatocyte PPARγ, where loss of this control explains in part the protection against steatosis observed after aLivPPARγkd.
Post-weaning rats on high-fat diet manifested all phenotypes of metabolic syndrome and increased hepatic steatosis, which are linked to increased hepatic and adipocyte PPARγ expression.
Based on these results, we propose that VPA may enhance OLA-induced hepatocyte steatosis through the upregulation of PPARγ- and CD36-dependent lipid uptake, TAG synthesis, and lipid droplet formation.
Currently, there is no approved pharmacological treatment for this disease, but improvement of insulin resistance using peroxisome proliferator-activated receptor-γ (PPARγ) agonists, such as thiazolidinediones (TZDs), has been shown to reduce steatosis and steatohepatitis effectively and to improve liver function in patients with obesity-related NAFLD.
Our results suggest that dietary supplement of isorhamnetin may be beneficial to prevent obesity and steatosis and PPARγ antagonists may be useful to treat hepatic steatosis.
In addition, an α-MG supplement up-regulated hepatic AMPK, SirT1, and PPARγ levels compared with the high-fat diet states, suggesting that α-MG regulates hepatic steatosis and obesity through the SirT1-AMPK and PPARγ pathways in high-fat diet-induced obese mice.
We found that the LXRα gene and its lipogenic targets PPAR-γ (peroxisome-proliferator-activated receptor-γ), SREBP (sterol-regulatory-element-binding protein)-1c, SREBP-2 and FAS (fatty acid synthase) were overexpressed in the liver of NAFLD and HCV patients who had steatosis.
The risk of steatosis was increased by carriage of I148M in PNPLA3, but only in patients with HCV genotypes non-3 (odds ratio [OR]=1.9, 95% confidence interval [CI]=1.6-2.3, p<0.001) and similar, albeit weaker associations were found for SNPs in peroxisome proliferator-activated receptor-γ (PPARG) and interleukin-28B (IL28B).
The transient induction of PAI-1 gene expression mediated by PPARγ in the fatty liver might be involved in the increased risk of cardiovascular events associated with thiazolidinediones in diabetic patients through decreasing fibrinolytic activity.
We specifically examined whether fatty liver and IR are modified by hepatic DNA methylation of the peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) and mitochondrial transcription factor A (TFAM) promoters, and also evaluated whether liver mitochondrial DNA (mtDNA) content is associated with NAFLD and IR.