FGF21
2022-09-03: reference:
FGF21 #
- Downstream of GCN2 (general control nonderepressible 2), I believe.
- Its kinase activity is activated under conditions of amino acid deprivation, resulting in repression of general protein synthesis.
- Elevated GCN4 stimulates expresion of amino acid biosynthetic genes
- Its kinase activity is activated under conditions of amino acid deprivation, resulting in repression of general protein synthesis.
- Overexpression extends lifespan
- Inhibits SREBP-1c. Activates UCP1.
- FGF21 is an endocrine signal of protein restriction
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The moderate essential amino acid restriction entailed by low-protein vegan diets may promote vascular health by stimulating FGF21 secretion
- LPVD may increase hepatic GCN2 activity, which functions as a gauge of amino acid status.
- FGF21 can lower LDL by at least 2 mechanisms: SREBP-2 inhibition, andor via upregulation of LDL receptors (via inhibition of a mechanism that promotes proteasomal degradation of LDL Receptor, which I think is technically SREBP-2 inhibition mediated so)
- Ultimately via something like inhibiting SREBP->LXR, whose activation induces IDOL (inducible degrader of LDLR).
- In regard to hepatic SREBP-1 expression, Lin’s group found no impact of FGF21 in mice: Fibroblast growth factor 21 prevents atherosclerosis by suppression of hepatic sterol regulatory element-binding protein-2 and induction of adiponectin in mice… In contrast, in a human liver-derived cell line, HepG2, FGF21 modestly decreased expression of SREBP-1c mRNA, and more substantially decreased the level of the mature processed protein; this effect could rationalize FGF21’s ability to suppress hepatic de novo lipogenesis.
- Ketogenic Diet Impairs FGF21 Signaling and Promotes Differential Inflammatory Responses in the Liver and White Adipose Tissue