Very low-carbohydrate diet with higher protein ratio improves lipid metabolism and inflammation in rats with diet-induced nonalcoholic fatty liver disease

I. Ting Wu, Wan Ju Yeh, Wen Chih Huang, Hsin Yi Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, and it is mainly treated through lifestyle modifications. The very low-carbohydrate diet (VLCD) can help lose weight rapidly but the possible effects of extreme dietary patterns on lipid metabolism and inflammatory responses in individuals with NAFLD remain debatable. Moreover, VLCD protein content may affect its effectiveness in weight loss, steatosis, and inflammatory responses. Therefore, we investigated the effects of VLCDs with different protein contents in NAFLD rats and the mechanisms underlying these effects. After a 16-week inducing period, the rats received an isocaloric normal diet (NC group) or a VLCD with high or low protein content (NVLH vs. NVLL group, energy ratio:protein/carbohydrate/lipid=20/1/79 vs. 6/1/93) for the next 8 weeks experimental period. We noted that the body weight decreased in both the NVLH and NVLL groups; nevertheless, the NVLH group demonstrated improvements in ketosis. The NVLL group led to hepatic lipid accumulation, possibly by increasing very-low-density lipoprotein receptor (VLDLR) expression and elevating liver oxidative stress, subsequently activating the expression of Nrf2, and inflammation through the TLR4/TRIF/NLRP3 and TLR4/MyD88/NF-κB pathway. The NVLH was noted to prevent the changes in VLDLR and the TLR4-inflammasome pathway partially. The VLCD also reduced the diversity of gut microbiota and changed their composition. In conclusion, although low-protein VLCD consumption reduces BW, it may also lead to metabolic disorders and changes in microbiota composition; nevertheless, a VLCD with high protein content may partially alleviate these limitations.

Original languageEnglish
Article number109583
JournalJournal of Nutritional Biochemistry
Volume126
DOIs
Publication statusPublished - 2024 Apr

Keywords

  • Gut microbiota
  • Inflammation
  • Non-alcoholic fatty liver disease
  • Protein
  • Steatosis
  • Very low-carbohydrate diet

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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