High Casein Diet Differentially Alters FGF21 Levels in Plasma and Cardiac Tissue in Rats

Abstract

Fibroblast growth factor‐21 (FGF21) is a cytokine that has been demonstrated to regulate metabolism and have cardioprotective effects in response to obesity and other cardiac stressors. High protein diets have been used to reduce body fat and ameliorate metabolic disorders, however the effects of high protein diets on FGF21‐mediated signaling in cardiac tissue are not well known. We hypothesized that high protein diets will increase circulating levels of FGF21, leading to enhanced FGF21‐mediated signaling in cardiac tissue. Male Sprague‐Dawley rats were placed into one of three dietary groups: 1) control diet (20% of kcal from protein; CON; n=8), 2) high soy protein diet (40% of kcal from soy; SOY; n=8), or high casein protein diet (40% of kcal from casein; CAS; n=8). Food consumption and body mass were recorded weekly. After 15 weeks, blood was collected and hearts were excised after an overnight fast. Western immunoblotting was performed on cardiac homogenates and analyzed for: FGF21, FGF receptor‐1 (FGFR1), phospho‐FGFR1Tyr654, phospho‐ERK1/2Thr202/Tyr204, phospho‐AktSer473, phospho‐AMPKThr172, phospho‐p38 MAPKThr180/Tyr182, and 4‐hydroxynonenal (4‐HNE), a marker of oxidative stress. There was no difference in daily food intake or terminal body mass between dietary groups. Plasma concentrations of FGF21 were significantly (P<0.05) greater for CAS (742.1±149.9 pg/ml) compared to CON (213.6±37.7 pg/ml), determined by ELISA. FGF21 protein levels in the heart were significantly (P<0.05) lower for CAS compared to CON and SOY groups. Phospho‐AktSer473 was significantly (P<0.05) greater in SOY compared to CON and CAS groups. There were no other significant differences between dietary groups for any other analyte measured. These data indicate that high protein diets composed of differing protein sources have non‐uniform effects on plasma and cardiac levels of FGF21. Additionally, 15‐weeks of high protein diet consumption does not appear to alter body mass or FGF21‐mediated signaling in the rat heart.Support or Funding InformationCentral Michigan University Herbert H. and Grace A. Dow College of Health Proffesions, and the Office of Research and Graduate Studies Early Career Award.