TY  - JOUR
AB  - Left ventricular hypertrophy (LVH) is associated with increased cardiac expression of fibroblast growth factor-23 (FGF23) in mice and men. To further elucidate the role of cardiac FGF23 in LVH, we specifically ablated Fgf23 in cardiomyocytes, and employed transverse aortic constriction (TAC) to induce LVH by pressure overload. LVH developed independently of cardiac FGF23, but cardiomyocyte-specific Fgf23 knock-out (Fgf23CKO) TAC mice were characterized by ameliorated hypertension and a distinct reduction of cardiac fibrosis, relative to Fgf23fl/fl TAC controls. Spatial metabolomics revealed reduced intracellular glucose abundance and lowered cardiac energy charge in Fgf23CKO TAC mice, whereas treatment of cultured cardiomyocytes with FGF23 increased intracellular glucose abundance. Spatial transcriptomics showed a downregulation of glucose transporters and glycolytic enzymes, but an upregulation of enzymes involved in fatty acid oxidation in Fgf23CKO TAC mice. These findings suggest that reduced cardiac FGF23 signaling promotes cardiac metabolic health by downregulating glucose consumption and favoring fatty acid oxidation. Created in https://BioRender.com.
AU  - Latic, N.*
AU  - Lari, A.*
AU  - Sun, N.
AU  - Zupcic, A.*
AU  - Oubounyt, M.*
AU  - Falivene, J.*
AU  - Buck, A.
AU  - Hofer, M.*
AU  - Chang, W.*
AU  - Kuebler, W.M.*
AU  - Baumbach, J.*
AU  - Walch, A.*
AU  - Grabner, A.*
AU  - Erben, R.G.*
C1  - 75914
C2  - 58188
TI  - Deletion of cardiac fibroblast growth factor-23 beneficially impacts myocardial energy metabolism in left ventricular hypertrophy.
JO  - npj Metab. Health Dis.
VL  - 3
IS  - 1
PY  - 2025
SN  - 2948-2828
ER  - 

TY  - JOUR
AB  - Dietary interventions constitute powerful approaches for disease prevention and treatment. However, the molecular mechanisms through which diet affects health remain underexplored in humans. Here, we compare plasma metabolomic and proteomic profiles between dietary states for a unique group of individuals who alternate between omnivory and restriction of animal products for religious reasons. We find that short-term restriction drives reductions in levels of lipid classes and of branched-chain amino acids, not detected in a control group of individuals, and results in metabolic profiles associated with decreased risk for all-cause mortality. We show that 23% of proteins whose levels are affected by dietary restriction are druggable targets and reveal that pro-longevity hormone FGF21 and seven additional proteins (FOLR2, SUMF2, HAVCR1, PLA2G1B, OXT, SPP1, HPGDS) display the greatest magnitude of change. Through Mendelian randomization we demonstrate potentially causal effects of FGF21 and HAVCR1 on risk for type 2 diabetes, of HPGDS on BMI, and of OXT on risk for lacunar stroke. Collectively, we find that restriction-associated reprogramming improves metabolic health and emphasise high-value targets for pharmacological intervention.
AU  - Rouskas, K.*
AU  - Bocher, O.
AU  - Simistiras, A.*
AU  - Emmanouil, C.*
AU  - Mantas, P.*
AU  - Skoulakis, A.*
AU  - Park, Y.-C.
AU  - Dimopoulos, A.*
AU  - Glentis, S.*
AU  - Kastenmüller, G.
AU  - Zeggini, E.
AU  - Dimas, A.S.
C1  - 74082
C2  - 57330
TI  - Periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on cardiometabolic health.
JO  - npj Metab. Health Dis.
VL  - 3
IS  - 1
PY  - 2025
SN  - 2948-2828
ER  -