Effects of lactoferrin on high-fat and high-cholesterol diet-induced non-alcoholic fatty liver disease in mice.

BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, representing a growing public health burden. While previous studies indicated that lactoferrin (LF) alleviates hepatic lipid accumulation, a hallmark of NAFLD, the mechanisms involved are still elusive. METHODS Male C57BL/6J mice were randomly divided into the control (CON), high-fat, high-cholesterol diet containing cholate (HFCCD), and HFCCD+LF groups and treated for 8 weeks' intervention. Liver and small intestine tissues were analyzed to investigate lipid metabolism and underlying mechanisms. Additionally, gut microbiota composition and short-chain fatty acid (SCFA) levels were assessed. RESULTS HFCCD feeding induced hepatic steatosis, while LF intervention improved lipid metabolism by reducing fatty acid synthesis and increasing lipolysis in the liver. Mechanistically, LF downregulated the protein expression of serotonin receptor 2A (HTR2A), which is related to lipogenesis, and upregulated the protein expression of peroxisome proliferator-activated receptor α (PPARα), which is one of the pivotal lipolytic genes, and its downstream effector, carnitine palmitoyl transferase-1A (CPT-1A), in the liver. Additionally, LF increased the relative abundance of gut microbiota related to glycolipid metabolism, such as Adlercreutzia, and decreased the relative abundance of 5-HT-promoting gut microbiota, such as Clostridia. Furthermore, LF increased the levels of SCFAs, which positively correlated with the relative abundance of Adlercreutzia. CONCLUSION Our study suggests that LF intervention alleviates HFCCD-induced NAFLD in mice, which is potentially associated with regulation of the HTR2A-PPARa-CPT-1A pathway and gut microbiota composition.

• Publication year

  2025

• Venue

  Journal of Nutritional Biochemistry

• Publication date

  2025-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.jnutbio.2025.109938PMID 40294723
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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