Thu, Mar-09-17, 09:10
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Senior Member
Posts: 15,075
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Plan: mostly milkfat
Stats: 190/152.4/154
BF:
Progress: 104%
Location: Ontario
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https://www.ncbi.nlm.nih.gov/pubmed/25736301
Quote:
Role of fibroblast growth factor 21 in the early stage of NASH induced by methionine- and choline-deficient diet.
Tanaka N1, Takahashi S2, Zhang Y3, Krausz KW2, Smith PB4, Patterson AD4, Gonzalez FJ5.
Author information
Abstract
Fibroblast growth factor 21 (FGF21) is a modulator of energy homeostasis and is increased in human nonalcoholic liver disease (NAFLD) and after feeding of methionine- and choline-deficient diet (MCD), a conventional inducer of murine nonalcoholic steatohepatitis (NASH). However, the significance of FGF21 induction in the occurrence of MCD-induced NASH remains undetermined. C57BL/6J Fgf21-null and wild-type mice were treated with MCD for 1 week. Hepatic Fgf21 mRNA was increased early after commencing MCD treatment independent of peroxisome proliferator-activated receptor (PPAR) α and farnesoid X receptor. While no significant differences in white adipose lipolysis were seen in both genotypes, hepatic triglyceride (TG) contents were increased in Fgf21-null mice, likely due to the up-regulation of genes encoding CD36 and phosphatidic acid phosphatase 2a/2c, involved in fatty acid (FA) uptake and diacylglycerol synthesis, respectively, and suppression of increased mRNAs encoding carnitine palmitoyl-CoA transferase 1α, PPARγ coactivator 1α, and adipose TG lipase, which are associated with lipid clearance in the liver. The MCD-treated Fgf21-null mice showed increased hepatic endoplasmic reticulum (ER) stress. Exposure of primary hepatocytes to palmitic acid elevated the mRNA levels encoding DNA damage-inducible transcript 3, an indicator of ER stress, and FGF21 in a PPARα-independent manner, suggesting that lipid-induced ER stress can enhance hepatic FGF21 expression. Collectively, FGF21 is elevated in the early stage of MCD-induced NASH likely to minimize hepatic lipid accumulation and ensuing ER stress. These results provide a possible mechanism on how FGF21 is increased in NAFLD/NASH.
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It seems to ge a general defense vs. fatty liver. So it's elevated in fatty liver. I don't know if this is a matter of "FGF21 resistance" or just a matter of the modern diet being sort of above its paygrade. I'm sure it means well.
Methionine and choline deficient diets--methionine and choline-rich diets both stand accused in some vegan circles of being deathogenic, methionine restriction studies in mice show increased longevity. And byproducts of choline metabolism by some gut bugs yields a substance (TMAO) that's accused of causing heart disease. A fair number of people are probably avoiding choline and methionine in their diet, I'm sure that will end well.
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