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This one provides genetically proxied evidence to support that FGF21 signaling may reduce chronic kidney disease risk, have favorable effects across a broad range of renal outcomes and cardiometabolic risk factors. 
- Fibroblast growth factor 21 (FGF21) is a fasting or stress inducible metabolic hormone produced mainly in the liver.
It plays important roles in regulating glucose and lipid homeostasis, as well as bone homeostasis.
It plays important roles in regulating glucose and lipid homeostasis, as well as bone homeostasis.
- This study leveraged a missense genetic variant, rs739320 in the FGF21 gene, that associates with magnetic resonance imaging-derived liver fat as a clinically validated and biologically plausible instrumental variable for studying the effects of FGF21 analogs.
- Performing Mendelian randomization, the study ascertained associations between instrumented FGF21 and kidney phenotypes, cardiometabolic disease risk factors, as well as the circulating proteome and metabolome.
- Analyses provided new genetic evidence that FGF21 signaling may reduce CKD risk and have favorable effects across a broad range of renal outcomes, including eGFR, urinary sodium excretion, BUN and UACR.
- Genetic support to support the notion that FGF21 may have a beneficial effect on fasting insulin and apolipoprotein B was also found.
- In line with previous Mendelian randomization studies, a favorable FGF21 effect was observed on waist-to-hip ratio, blood pressure, LDL-c and triglycerides.
- In contrast, a lack of association with HDL-c contrasts findings from studies and trials.
- Proteomics analyses supported a similar reduction in proteins involved in triglyceride and fat metabolism, e.g., pancreatic lipase-related protein 2, pancreatic triacylglycerol lipase, lipase cofactor colipase, and cholecystokinin.
- Interestingly, an association between higher genetically proxied FGF21 and lower alcohol consumption and higher protein intake was also observed.
Renoprotective effects of genetically proxied fibroblast growth factor 21: Mendelian randomization, proteome-wide and metabolome-wide association study (open access)
doi.org/10.1016/j.meta…
#nutrition #diet #MetabolicSyndrome #CKD #FGF21
doi.org/10.1016/j.meta…
#nutrition #diet #MetabolicSyndrome #CKD #FGF21
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