The associations of dietary folate and serum folate with lipid profiles: findings from the national health and nutrition examination survey 2011–2016

Feng, Yunfu; Chen, Xiaohua; Pan, Ying; Yang, Yefeng

doi:10.1186/s12944-023-01793-4

Cited by 4 publications

(1 citation statement)

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“…Liver is the primary organ responsible for lipid metabolism and folate storage. Notably, serum folate levels have been associated with lipid profiles, highlighting the significance of folate in hepatic lipid metabolism [ 7 ]. Folate serves as a one-carbon carrier in folate-mediated one-carbon metabolism (OCM), contributing to the biosynthesis and metabolism of nucleic acids, proteins, amino acids, neurotransmitters, and certain vitamins (Fig.…”

Section: Introductionmentioning

confidence: 99%

Disturbed intracellular folate homeostasis impairs autophagic flux and increases hepatocytic lipid accumulation

Chi,

Lee,

Tang

et al. 2024

BMC Biol

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Background Metabolic associated fatty liver disease (MAFLD), a prevalent liver disorder affecting one-third of the global population, encompasses a spectrum ranging from fatty liver to severe hepatic steatosis. Both genetic and lifestyle factors, particularly diet and nutrition, contribute to its etiology. Folate deficiency, a frequently encountered type of malnutrition, has been associated with the pathogenesis of MAFLD and shown to impact lipid deposition. However, the underlying mechanisms of this relationship remain incompletely understood. We investigated the impact of disturbed folate-mediated one-carbon metabolism (OCM) on hepatic lipid metabolism both in vitro using human hepatoma cells and in vivo using transgenic fluorescent zebrafish displaying extent-, stage-, and duration-controllable folate deficiency upon induction. Results Disturbed folate-mediated one-carbon metabolism, either by inducing folate deficiency or adding anti-folate drug, compromises autophagy and causes lipid accumulation in liver cells. Disturbed folate status down-regulates cathepsin L, a key enzyme involved in autophagy, through inhibiting mTOR signaling. Interfered mitochondrial biology, including mitochondria relocation and increased fusion-fission dynamics, also occurs in folate-deficient hepatocytes. Folate supplementation effectively mitigated the impaired autophagy and lipid accumulation caused by the inhibition of cathepsin L activity, even when the inhibition was not directly related to folate deficiency. Conclusions Disruption of folate-mediated OCM diminishes cathepsin L expression and impedes autophagy via mTOR signaling, leading to lipid accumulation within hepatocytes. These findings underscore the crucial role of folate in modulating autophagic processes and regulating lipid metabolism in the liver.

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Section: Introductionmentioning

confidence: 99%