Background: In recent years, with the change in human dietary habits, hyperlipidemia (HLP) has become a common chronic disease. Hyperlipidemia is closely related to the incidence of cardiovascular diseases. Due to the increasing incidence and mortality from cardiovascular diseases, it is imperative to develop new medications for reducing lipid levels. With the aim of discovering new treatment options for hyperlipidemia, we conducted a multi-omics analysis of a potential endogenous bile acid compound.
Methods: Two hyperlipidemia models were established by feeding rats and mice with a high-fat diet. Serum and fecal specimens of rats with hyperlipidemia were collected. Through the combined analysis of lipid metabolism sequencing, 16S RNA intestinal flora sequencing, and bile acid targeted metabolism sequencing, taurohyodeoxycholic acid (THDCA) was found to be a potential lipid-lowering compound. A mouse hyperlipidemia model was developed to verify the anti-hyperlipidemia function of THDCA.
Results: Analysis of serum lipid metabolites revealed that the synthesis of bile acid was one of the metabolic pathways that showed significant alterations. 16S RNA sequencing of intestinal flora also found that high-fat diet intake greatly influenced both primary and secondary bile acid biosynthesis. Analysis of bile acid metabolites in the serum and liver tissue found that THDCA in the secondary bile acids is a potential biomarker of hyperlipidemia. Verification experiments in mice confirmed the beneficial function of THDCA in lowering abnormal lipid levels induced by a high-fat diet.
Conclusions: THDCA has been identified as a biomarker of hyperlipidemia and has shown potential for the treatment of hyperlipidemia.
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http://dx.doi.org/10.31083/j.rcm2409248 | DOI Listing |
Expert Opin Drug Metab Toxicol
January 2025
Institut de R&D Servier, Paris-Saclay, F-91190 Gif-sur-Yvette, France.
Introduction: Drug-mediated inhibition of bile salt efflux transporters may cause liver injury. In vitro prediction of drug effects toward canalicular and/or sinusoidal efflux of bile salts from human hepatocytes is therefore a major issue, which can be addressed using liver cell-based assays.
Area Covered: This review, based on a thorough literature search in the scientific databases PubMed and Web of Science, provides key information about hepatic transporters implicated in bile salt efflux, the human liver cell models available for investigating functional inhibition of bile salt efflux, the different methodologies used for this purpose, and the modes of expression of the results.
J Biol Chem
January 2025
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 02447, Seoul, Korea; Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 02447, Seoul, Korea; Kyung Hee Institute of Convergence Korean Medicine, Kyung Hee University, 02447, Seoul, Korea. Electronic address:
FXR, encoded by Nh1r4, is a nuclear receptor crucial in regulating bile acid, lipid, and glucose metabolism. Prior research has indicated that activating FXR in the liver and small intestine may offer protection against obesity and metabolic diseases. This study demonstrates the essential role of the FXR-ApoC2 pathway in promoting the browning of white adipose tissue (WAT).
View Article and Find Full Text PDFClin Nutr ESPEN
January 2025
Department of Critical Care Medicine, The affiliated hospital of Qingdao University, 1677 Wutaishan Road, Qingdao, Shandong, 266000, China. Electronic address:
Background: Gut microbiota disturbance may worsen critical illnesses and is responsible for the progression of multiple organ dysfunction syndrome. In our previous study, there was a trend towards a higher α-diversity of the gut microbiota in sequential feeding (SF) than in continuous feeding (CF) for critically ill patients. We designed this non-blinded, randomized controlled study to confirm these results.
View Article and Find Full Text PDFCell Rep Med
December 2024
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR, China; State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hong Kong SAR, China; Research Institute for Future Food, The Hong Kong Polytechnic University, Hong Kong SAR, China. Electronic address:
Immune checkpoint inhibitors are not effective for metabolic dysfunction-associated fatty liver disease (MAFLD)-hepatocellular carcinoma (HCC) patients, and identifying the key gut microbiota that contributes to immune resistance in these patients is crucial. Analysis using 16S rRNA sequencing reveals a decrease in Akkermansia muciniphila (Akk) during MAFLD-promoted HCC development. Administration of Akk ameliorates liver steatosis and effectively attenuates the tumor growth in orthotopic MAFLD-HCC mouse models.
View Article and Find Full Text PDFFood Chem
January 2025
College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China. Electronic address:
Herein, we developed multifunctional hydrogels formed between soybean protein (SPI)-gallic acid conjugate and oxidized dextran (ODex) via a Schiff base reaction. The effects of ODex on the morphology, structure, and functional properties of the hydrogels were elucidated. The results showed that the crosslinking modes in the hydrogels include hydrogen bonding, Schiff bases, Michael addition, and π-π stacking.
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