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Cited by 20Liver Disease Diagnosis and TreatmentFolate and B Vitamins ResearchDiet, Metabolism, and Disease

Effects of riboflavin deficiency and high dietary fat on hepatic lipid accumulation: a synergetic action in the development of non-alcoholic fatty liver disease

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Wang, Yanxian, Bian, Xiangyu, Wan, Min, Dong, Weiyun, Gao, Weina, Yao, Zhanxin, Guo, Changjiang·2024·Nutrition & Metabolism
DOI 10.1186/s12986-023-00775-8PMC PMC10763341
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Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Riboflavin, one of water soluble vitamins, plays a role in lipid metabolism and antioxidant function. However, the effects of riboflavin deficiency on NAFLD development have not yet to be fully explored. Methods: In the present study, an animal model of NAFLD was induced by high fat diet feeding in mice and a cellular model of NAFLD was developed in HepG2 cells by palmitic acid (PA) exposure. The effects of riboflavin deficiency on lipid metabolism and antioxidant function were investigated both in vivo and in vitro. In addition, the possible role of peroxisome proliferator-activated receptor gamma (PPARγ) was studied in HepG2 cells using gene silencing technique. Results: The results showed that riboflavin deficiency led to hepatic lipid accumulation in mice fed high fat diet. The expressions of fatty acid synthase (FAS) and carnitine palmitoyltransferase 1 (CPT1) were up-regulated, whereas that of adipose triglyceride lipase (ATGL) down-regulated. Similar changes in response to riboflavin deficiency were demonstrated in HepG2 cells treated with PA. Factorial analysis revealed a significant interaction between riboflavin deficiency and high dietary fat or PA load in the development of NAFLD. Hepatic PPARγ expression was significantly upregulated in mice fed riboflavin deficient and high fat diet or in HepG2 cells treated with riboflavin deficiency and PA load. Knockdown of PPARγ gene resulted in a significant reduction of lipid accumulation in HepG2 cells exposed to riboflavin deficiency and PA load. Conclusions: There is a synergetic action between riboflavin deficiency and high dietary fat on the development of NAFLD, in which PPARγ may play an important role.

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  • Metabolites that were lower in 4s2M (riboflavin, benzaldehyde, 1-aminocyclopropane-1-carboxylic acid) are not primary intermediates of central carbon metabolism and changes in their abundance may reflect shifts in cofactor handling or dietary metabolite uptake rather than broad changes in core metabolic pathways.

    “Metabolites that were lower in 4s2M - riboflavin, benzaldehyde, and 1-aminocyclopropane-1-carboxylic acid – are not primary intermediates of central carbon metabolism and changes in their abundance may reflect shifts in cofactor handling or dietary metabolite uptake rather than broad changes in core metabolic pathways”

    From Older adult APOE4 mice exhibit modest immunometabolic adaptation following microglial APOE2 replacement (2027) · cites this paper as Wang et al., 2024

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Cited by

Sorted by citations

Authors
Wang, Y., Bian, X., Wan, M., Dong, W., Gao, W., Yao, Z., & Guo, C.
Corresponding author
Guo, Changjiang
ORCID
Venue
Nutrition & Metabolism
Publisher
Springer Science and Business Media LLC
Published
2024-01-02
Volume
21
Issue
1
Pages
1-1
ISSN
1743-7075 (ISSN-L)
DOI
10.1186/s12986-023-00775-8
PMC
PMC10763341
OpenAlex
W4390508831
Cited by
20
References
5
Citations by year
2026: 5 · 2025: 11 · 2024: 4
FWCI
5.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrition & Metabolism (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (No. 81973029)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
non-alcoholic fatty liver disease, riboflavin deficiency, high-fat diet, hepatic lipid accumulation, PPARγ, palmitic acid, fatty acid synthase, carnitine palmitoyltransferase 1, adipose triglyceride lipase, lipid metabolism, antioxidant function, synergistic interaction

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