P765 - PLANT-BASED PROTEIN DIGESTATES FROM PEA AND FAVA BEANS ENHANCE INTESTINAL FGF19 SYNTHESIS PARTLY VIA PPARΓ ACTIVATION: IMPLICATIONS FOR MUSCLE HEALTH AND METABOLIC REGULATION

P765

PLANT-BASED PROTEIN DIGESTATES FROM PEA AND FAVA BEANS ENHANCE INTESTINAL FGF19 SYNTHESIS PARTLY VIA PPARΓ ACTIVATION: IMPLICATIONS FOR MUSCLE HEALTH AND METABOLIC REGULATION

C. Lefranc-Millot¹, C. Defois-Fraysse ^2,3, B. Benoit³, A. Jalabert³, A. Beau³, L. Brunet³, F. Ringard¹, C. Perreau^1,*, H. Vidal³

¹R&D Life Sciences, Roquette, Lestrem, ²R&D, Greencell, Saint-Beauzire, ³Carmen, Pierre-Bénite, France

Rationale: Plant-based proteins are increasingly recognized as alternatives to animal proteins for muscle synthesis and sarcopenia prevention. This study investigated whether plant protein digestates (PDs) modulate intestinal Fibroblast Growth Factor 19 (FGF19) synthesis, a key muscle mass and strength regulator, also playing a crucial role in regulating bile acid, glucose, and lipid metabolism.

Methods: Confluent HT29 human intestinal cells were exposed to Pea and Fava Bean PDs (NUTRALYS^®,1 mg/mL), the FXR agonist GW4064 (0.1 µM), or rosiglitazone (PPARγ activator, 50 nM). FGF19 secretion was measured by ELISA, while FXR gene (NR1H4) expression and FXR protein levels were analyzed by RT-qPCR and western blotting, respectively. Data were expressed as mean ± SEM and analyzed using one-way ANOVA with Tukey’s post hoc test.

Results: PDs enhanced the effect of GW4064 by shifting its dose–response curve and lowering its EC50 for FGF19 induction. In combination with GW4064, PDs slightly increased NR1H4 expression. Rosiglitazone strongly upregulated FGF19 and NR1H4 expression when combined with GW4064. This effect was abolished by the PPARγ inhibitor GW9662, confirming PPARγ signaling involvement. The combination of PDs, GW4064, and GW9662 reduced FGF19 mRNA and protein levels without significantly affecting NR1H4 expression.

Conclusion: Pea and Fava Bean protein digestates, as Rosiglitazone (pure PPARγ agonist), but at higher doses, enhance FXR-dependent FGF19 production, via PPARγ activation of NR1H4 expression in human intestinal cells. PPARγ is also known as a key regulator of adipogenesis and lipid storage, and a therapeutic target of type 2 diabetes. These PDs, as potential natural PPARγ activators, could therefore open new perspectives in the context of complex metabolic disorders prevention.

Disclosure of Interest: C. Lefranc-Millot Grant / Research Support from: This research was funded by ROQUETTE to which the author belongs., C. Defois-Fraysse : None declared, B. Benoit: None declared, A. Jalabert: None declared, A. Beau: None declared, L. Brunet: None declared, F. Ringard Grant / Research Support from: This research was funded by Roquette, to which the author belongs., C. Perreau Grant / Research Support from: This research was funded by ROQUETTE to which the author belongs., H. Vidal: None declared