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An 8-Week Very Low-Calorie Ketogenic Diet (VLCKD) Alters the Landscape of Obese-Derived Small Extracellular Vesicles (sEVs), Redefining Hepatic Cell Phenotypes.

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  • معلومة اضافية
    • المصدر:
      Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Basel, Switzerland : MDPI Publishing
    • الموضوع:
      Diet, Ketogenic*/methods ; Extracellular Vesicles*/metabolism ; Hepatocytes*/metabolism ; Obesity*/diet therapy ; Phenotype* ; Liver Cirrhosis*/diet therapy; Humans ; Male ; Female ; Adult ; Middle Aged ; Caloric Restriction/methods ; Cell Line ; Liver/metabolism ; Liver/pathology ; Autophagy
    • نبذة مختصرة :
      Background. Very low-calorie ketogenic diets (VLCKD) are an effective weight-loss strategy for obese individuals, reducing risks of liver conditions such as non-alcoholic steatohepatitis and fibrosis. Small extracellular vesicles (sEVs) are implicated in liver fibrosis by influencing hepatic cell phenotypes and contributing to liver damage. This study investigates sEVs derived from serum of 60 obese adults categorized into low fibrosis risk (LR) and intermediate/high fibrosis risk (IHR) groups based on FibroScan elastography (FIB E scores, limit value 8 kPa) and all participants underwent an 8-week VLCKD intervention. Methods. The study examines the impact of these sEVs on fibrosis markers, inflammation, and autophagy in a hepatocyte cell line (HEPA-RG) using bioinformatics, RNA sequencing, lipidomics, RT-PCR, and Western blotting before (T0) and after (T1) VLCKD. Results. sEVs from LR patients post-VLCKD reduced fibrosis related gene expression (e.g., ACTA2) and enhanced proteins associated with regeneration and inflammation (e.g., HDAC6). Conversely, sEVs from IHR patients increased fibrosis and inflammation related gene expression (PIK3CB, AKT1, ACTA2) in hepatocytes, raising concerns about VLCKD suitability for IHR patients. IHR sEVs also decreased expression of HDAC10, HDAC6, HDAC3, MMP19, and MMP2, while increasing modulation of p-AKT, α-SMA, and VIM. Conclusion. These findings underscore the critical role of sEVs in regulating inflammation, remodeling, and hepatic stress responses, particularly in IHR patients, and suggest sEVs could complement instrumental evaluations like FibroScan in fibrosis assessment.
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    • Grant Information:
      Ricerca 2024 (DDG 851/23) Italian Ministry of Heath
    • Contributed Indexing:
      Keywords: VLCKD; fibrosis; liver disease; obesity; small extracellular vesicles
    • الموضوع:
      Date Created: 20241217 Date Completed: 20241217 Latest Revision: 20250104
    • الموضوع:
      20250104
    • الرقم المعرف:
      PMC11643994
    • الرقم المعرف:
      10.3390/nu16234189
    • الرقم المعرف:
      39683581