Role of prokineticins and T-reg cells in obesity-associated metabolic oxidative dysregulation in NAFLD

We investigate the role of prokineticin, T-reg cells, and oxidative metabolism in the progression of obesity-related NASH to HCC. Our findings on a cohort of 250 patients, including Obese NAFLD and Non-Obese NAFLD, reveal significant insights. In Obese NAFLD, PK-1 mRNA expression was reduced by 2.4-...

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Bibliographic Details
Published in:Scientific reports Vol. 15; no. 1; pp. 29470 - 14
Main Authors: Prakash, Shyam, Priyatma, Aasarey, Ram, Khan, Shahid, Vikram, Naval K., Shalimar, Medha, Srivastava, Saumya, Pandey, Shivam, Priya, Akanksha, Aggarwal, Sandeep
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 12.08.2025
Nature Publishing Group
Nature Portfolio
Subjects:
692/4017
692/4020
692/53
Adipocytes
Adult
Blood diseases
Blood pressure
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
CD4 antigen
CD8 antigen
Correlation analysis
Cytokines
Diabetes
Enzymes
Fatty acid-binding protein
Fatty acids
Fatty liver
Female
Flow cytometry
GA-binding protein
Gastrointestinal Hormones - genetics
Gastrointestinal Hormones - metabolism
Gene expression
Glucose
High density lipoprotein
Humanities and Social Sciences
Humans
Hypertension
Immunomodulation
Interleukin 10
Interleukin-10 - genetics
Interleukin-10 - metabolism
Liver cirrhosis
Liver diseases
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Male
Metabolic disorders
Metabolic syndrome
Middle Aged
multidisciplinary
Neuropeptides
Non-alcoholic Fatty Liver Disease - etiology
Non-alcoholic Fatty Liver Disease - immunology
Non-alcoholic Fatty Liver Disease - metabolism
Non-alcoholic Fatty Liver Disease - pathology
Obesity
Obesity - complications
Obesity - immunology
Obesity - metabolism
Overweight
Oxidative metabolism
Oxidative Stress
Patients
Plasma
Science
Science (multidisciplinary)
Standard scores
Therapeutic targets
Vascular Endothelial Growth Factor, Endocrine-Gland-Derived - genetics
Vascular Endothelial Growth Factor, Endocrine-Gland-Derived - metabolism
Womens health
ISSN:2045-2322, 2045-2322
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Summary:We investigate the role of prokineticin, T-reg cells, and oxidative metabolism in the progression of obesity-related NASH to HCC. Our findings on a cohort of 250 patients, including Obese NAFLD and Non-Obese NAFLD, reveal significant insights. In Obese NAFLD, PK-1 mRNA expression was reduced by 2.4-fold ( p  < 0.01) compared to Non-Obese NAFLD, while PK-2 was upregulated by 1.4-fold ( p  < 0.005), and FABP-5 increased by 1.4-fold ( p  < 0.005) compared to T2DM. IL-10 mRNA expression was 2.4-fold higher ( p  < 0.005) in MetS verses to Non-Obese NAFLD. Nrf-2 expression was elevated by 1.13-fold in Non-Obese NAFLD compared to Obese NAFLD ( p  < 0.05). Flow cytometric analysis of T-reg cells was three times lower in Obese NAFLD compared to MetS ( p  < 0.005), with a notable reduction in CD8 + cells and an increase in CD4 + cells. Correlation analysis in Obese NAFLD revealed strong positive correlations between IL-10 and T-reg ( r  = 1), CD4 + ( r  = 0.99), and CD8 + cells ( r  = 0.99). PK-1 expression correlated with CD8 + cells ( r  = 0.52), while PK-2 negatively correlated with C-type lectin ( r =-0.49). FABP-5 exhibited significant positive correlations with PK-1 ( r  = 0.54) and IL-10 ( r  = 0.63). We highlight the interplay between prokineticins, immune modulation, and metabolic oxidative factors to offer potential therapeutic targets to prevent progression to HCC, instilling hope for the future of NASH treatment.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-025-97969-2