Protein Restriction Increases Liver Fibroblast Growth Factor 21 Expression in Growing Pigs

Fibroblast growth factor 21 (FGF21) is a liver-derived hormone which regulates glucose metabolism, energy expenditure, and body weight. FGF21 was originally described as a fasting hormone, but recent work in rodent models and humans suggests that FGF21 is specifically induced by the restriction of dietary protein rather than energy restriction. To determine whether this protein-specific effect also translated to young, growing pigs, the effect of a low-protein diet on the expression of liver Fgf21 mRNA expression was examined. All pigs were housed in the University of Wisconsin-Platteville Swine Center (Platteville, WI) and all procedures were approved by the University of Wisconsin-Platteville Animal Care and Use Committee. Sixteen four-week old crossbred barrows (mean BW 7.0 ± 0.1 kg) were randomly sorted into two pens (n = 8/pen) and assigned to one of two experimental diets, corn-soybean meal based (CON) and corn based (LP). Diets were formulated to be similar in NE, digestible Ca, and digestible P, but different in crude protein concentration (6.6 % LP versus 23.5 % CON as fed basis). Diets were fed ad libitum for 7 d using self-feeders. On day seven, all pigs were euthanized; serum and liver samples were collected and frozen for subsequent analysis. Consistent with a state of protein restriction, blood urea nitrogen concentrations were reduced in pigs fed LP versus CON diets (6.31 ± 1.22 mg/dL versus 13.66 ± 1.22 mg/dL; P < 0.001). Total liver RNA was extracted and Fgf21 mRNA expression was evaluated using real-time PCR. Fgf21 mRNA levels were increased seven-fold in pigs fed LP versus CON diets (7.4 ± 1.0 AU versus 1.0 ± 0.2 AU; P < 0.001). This increase is consistent with previous experiments in rodents and humans, suggesting that FGF21 is a novel signal of dietary protein restriction across multiple species. The current experiment provides a foundation for future studies examining the role of FGF21 as an endocrine regulator during periods of nutrient restriction in swine.