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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Vydané v:	Scientific reports Ročník 15; číslo 1; s. 29470 - 14
Hlavní autori:	Prakash, Shyam, Priyatma, Aasarey, Ram, Khan, Shahid, Vikram, Naval K., Shalimar, Medha, Srivastava, Saumya, Pandey, Shivam, Priya, Akanksha, Aggarwal, Sandeep
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 12.08.2025 Nature Publishing Group Nature Portfolio
Predmet:	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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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-025-97969-2