APS treatment suppressed abnormal glycolipid metabolism and insulin resistance following 8 weeks of catch‑up growth by improving hepatic SIRT1‑PPARα‑FGF21 intracellular signaling and reducing chronic inflammation, and by partially attenuating hepatic steatosis.
Equally, repressed expression of the B-lymphocyte chemoattractant CXCL13 and STAT4 as well as induced FGF21 evidenced amelioration of steatosis-related inflammation.
FGF21 depletion exacerbated alcohol-induced hepatic steatosis and liver injury, which was associated with increased activation of genes involved in lipogenesis mediated by SREBP1c and decreased expression of genes involved in fatty acid β-oxidation mediated by PGC1α. rhFGF21 administration reduced alcohol-induced hepatic steatosis and inflammation in WT mice.
Chronic treatment with recombinant FGF21 reduces serum and hepatic triglyceride levels and ameliorates fatty liver in obese mice, through the suppression of the lipogenic gene, Srebp-1.
Both hepatic PCK1 and plasma FGF21 correlated strongly and inversely with hepatic TG content, suggesting a key role for PCK1 and increased gluconeogenesis in resolving steatosis with a high-protein diet, with FGF21 expression reflecting declining cell stress.
ACC DKI mice had improved glucose and insulin tolerance and a reduction in body weight, body fat and hepatic steatosis similar to WT mice in response to FGF21 administration.
There was a tendency towards higher levels of hepatic FGF21 mRNA in patients with lobular inflammation and fibrosis and towards lower levels in the case of hepatocyte ballooning and steatosis.
FGF21 decreases in association with reductions in liver fat, GGT, and FIB4, suggesting that FGF21 is upregulated in the context of steatosis and steatohepatitis and is reduced when these conditions improve.
Moreover, by using a neutralizing antibody against FGF21, Fgf21-null mice and by treating mice with recombinant FGF21, we show that FGF21 may protect against hepatic steatosis by attenuating endoplasmic reticulum (ER) stress-induced VLDLR upregulation.
This corresponds to an induction of FGF21, which is required for long-term steatosis protection, as FGF21KO mice are refractory to the improved metabolic effects.
Here, we show that chronic PD retards the development of hypertrigylceridemia and fatty liver in obesity and that this relies on the induction of the hepatokine fibroblast growth factor 21 (FGF21).