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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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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Abstract	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.
AbstractList	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. 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. 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. Abstract 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. 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.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.
ArticleNumber	29470
Author	Priyatma Khan, Shahid Aasarey, Ram Pandey, Shivam Shalimar Priya, Akanksha Prakash, Shyam Medha Vikram, Naval K. Aggarwal, Sandeep Srivastava, Saumya
Author_xml	– sequence: 1 givenname: Shyam surname: Prakash fullname: Prakash, Shyam email: prakashaiims@gmail.com organization: Department of Laboratory Medicine, All India Institute of Medical Sciences, Department of Laboratory Medicine, All India Institute of Medical Sciences – sequence: 2 surname: Priyatma fullname: Priyatma organization: Department of Laboratory Medicine, All India Institute of Medical Sciences – sequence: 3 givenname: Ram surname: Aasarey fullname: Aasarey, Ram organization: Department of Laboratory Medicine, All India Institute of Medical Sciences – sequence: 4 givenname: Shahid surname: Khan fullname: Khan, Shahid organization: Department of Laboratory Medicine, All India Institute of Medical Sciences – sequence: 5 givenname: Naval K. surname: Vikram fullname: Vikram, Naval K. organization: Department of Medicine, All India Institute of Medical Sciences – sequence: 6 surname: Shalimar fullname: Shalimar organization: Department of Gastroenterology & Human Nutrition, All India Institute of Medical Sciences – sequence: 7 surname: Medha fullname: Medha organization: Department of Laboratory Medicine, All India Institute of Medical Sciences – sequence: 8 givenname: Saumya surname: Srivastava fullname: Srivastava, Saumya organization: Department of Laboratory Medicine, All India Institute of Medical Sciences – sequence: 9 givenname: Shivam surname: Pandey fullname: Pandey, Shivam organization: Department of Biostatistics, All India Institute of Medical Sciences – sequence: 10 givenname: Akanksha surname: Priya fullname: Priya, Akanksha organization: Department of Laboratory Medicine, All India Institute of Medical Sciences – sequence: 11 givenname: Sandeep surname: Aggarwal fullname: Aggarwal, Sandeep organization: Department of Surgical Disciplines, All India Institute of Medical Sciences
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SubjectTerms	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
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Title	Role of prokineticins and T-reg cells in obesity-associated metabolic oxidative dysregulation in NAFLD
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