Differential effects of protein intake versus intake of a defined oligopeptide on FGF-21 in obese human subjects in vivo.

BACKGROUND: FGF-21 is described as a powerful metabolic regulator with beneficial effects including glucose-lowering and improvement of insulin sensitivity without hypoglycaemia. On the other hand, FGF-21 is activated when muscle and other tissues are stressed by external effects or internal cellular pathogens that lead to shortcomings in metabolic balance. Previous results suggested that FGF-21 could be a promising target to develop future metabolic therapeutics. PURPOSE: The present study was performed to gain deeper insight into the regulation of FGF-21 by protein metabolism in obese human subjects. METHODS: FGF-21 serum concentrations were measured in a cohort of n = 246 obese humans ± type 2 diabetes mellitus (T2DM) (median age 53.0 [46.0; 60.0] years and BMI 40.43 [35.11; 47.24] kg/m2) and related to the nutritional protein intake. In addition, the effect of a novel oligopeptide purified from a ß-casein hydrolysate on FGF-21 was examined in vitro in liver cells and in vivo in a human intervention study with the main focus on metabolic inflammation including 40 mainly obese subjects (mean age 41.08 ± 9.76 years, mean BMI 38.29 ± 9.4 kg/m2) in a randomized 20 weeks double-blind cross-over design. MAIN FINDINGS: In the cohort analysis, FGF-21 serum concentrations were significant lower with higher protein intake in obese subjects without T2DM but not in obese subjects with T2DM. Furthermore, relative methionine intake was inversely related to FGF-21. While global protein intake in obesity was inversely associated with FGF-21, incubation of HepG2 cells with a ß-casein oligopeptide increased FGF-21 expression in vitro. This stimulatory effect was also present in vivo, since in the clinical intervention study treatment of obese subjects with the ß-casein oligopeptide for 8 weeks significantly increased FGF-21 serum levels from W0 = 23.86 pg/mL to W8 = 30.54 pg/mL (p < 0.001), while no increase was found for placebo. CONCLUSION: While the total nutritional protein intake is inversely associated with FGF-21 serum levels, a purified and well characterised oligopeptide is able to induce FGF-21 serum levels in humans. These findings suggest a differential role of various components of protein metabolism on FGF-21, rather than this factor being solely a sensor of total nutritional protein intake.

Generation and identification of anti-inflammatory peptides from bovine ß-casein using enzyme preparations from cod and hog.

BACKGROUND: The aim of the present study was to generate and identify potential anti-inflammatory peptides from bovine ß-casein with enzyme preparations from cod and hog. Furthermore, the potential of cod trypsin, derived from fishery by-products, to produce these bioactive peptides for replacement of non-food-grade tosyl phenylalanyl chloromethyl ketone (TPCK)-treated porcine trypsin enzyme preparation was evaluated. RESULTS: Potential anti-inflammatory peptides were obtained by hydrolysis of ß-casein with the tryptic enzyme preparations cod trypsin, porcine trypsin (TPCK-treated) and a porcine trypsin and chymotrypsin preparation (PTN 6.0 S). Proteolysates generated with enzyme preparations containing mainly chymotryptic activity (Cryotin, Cryotin F) did not exhibit any effect. CONCLUSION: The more chymotryptic enzyme activity is present, the lower is the potential anti-inflammatory activity of the hydrolysates in HEK(nfκb-RE) cells. Comparable peptides were produced by application of porcine trypsin (TPCK) and cod trypsin. Therefore, the enzyme preparation cod trypsin can replace the non-food-grade porcine enzyme preparation trypsin (TPCK) for the generation of potential anti-inflammatory peptides from ß-casein.