Elevated Serum Fibroblast Growth Factor 21 in Humans with Acute Pancreatitis

Abstract

BackgroundThe metabolic regulator Fibroblast Growth Factor 21 (FGF21) is highly expressed in the acinar pancreas, but its role in pancreatic function is obscure. It appears to play a protective role in acute experimental pancreatitis in mice. The aim of this study was to define an association between FGF21 and the course and resolution of acute pancreatitis in humans.Methods and Principal FindingsTwenty five subjects with acute pancreatitis admitted from May to September 2012 to the Beth Israel Deaconess Medical Center (BIDMC) were analyzed. Serial serum samples were collected throughout hospitalization and analyzed for FGF21 levels by ELISA. Twenty healthy subjects sampled three times over a four week period were used as controls. We found that, in patients with pancreatitis, serum FGF21 rises significantly and peaks four to six days after the maximum lipase level, before slowly declining. Maximum FGF21 levels were significantly greater than baseline levels for acute pancreatitis subjects (1733 vs. 638 pg/mL, P = 0.003). This maximum value was significantly greater than the highest value observed for our control subjects (1733 vs. 322 pg/mL, P = 0.0002). The ratio of active to total FGF21 did not change during the course of the disease (42.5% vs. 44.4%, P = 0.58). Fold increases in FGF21 were significantly greater in acute pancreatitis subjects than the fold difference seen in healthy subjects (4.7 vs. 2.0, P = 0.01). Higher fold changes were also seen in severe compared to mild pancreatitis (18.2 vs. 4.4, P = 0.01). The timing of maximum FGF21 levels correlated with day of successful return to oral intake (R2 = 0.21, P = 0.04).ConclusionsOur results demonstrate that serum FGF21 rises significantly in humans with acute pancreatitis. The pancreas may be contributing to increased FGF21 levels following injury and FGF21 may play a role in the recovery process.

Increased fructose consumption has sex‐specific effects on fibroblast growth factor 21 levels in humans

“…The observed stability of this ratio is consistent with the finding that the intact‐to‐total FGF21 ratio did not change in patients with acute pancreatitis, even though these individuals had significantly higher circulating levels compared with controls . It therefore appears that higher FGF21 levels are associated with higher cleavage of FGF21, thereby maintaining the same intact‐to‐total ratio, although neither of these studies included measurement of FAP levels.…”

Fibroblast growth factor 21 and fructose dynamics in humans

“…Several cross‐sectional studies have shown that FGF21 levels are increased in obesity and metabolic disease , suggesting the possibility of an FGF21‐resistant state, similar to obesity‐induced insulin and leptin resistance. Elevated FGF21 levels have also been reported in other acute inflammatory states including sepsis and pancreatitis .…”

A Dozen Years of Discovery: Insights into the Physiology and Pharmacology of FGF21

“…Conversely, pharmacologic administration or transgenic overexpression of FGF21 protected the pancreas against ER stress, inflammation and injury in mouse models of pancreatitis (Coate et al, 2017;Johnson et al, 2009Johnson et al, , 2014. In humans, the resolution of acute pancreatitis is correlated with increasing levels of circulating FGF21, further suggesting that FGF21 plays a protective role (Shenoy et al, 2016). These studies suggest a potential pharmacologic role for FGF21 in preventing and treating pancreatitis.…”