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Comprehensive proteomic analysis reveals omega-3 fatty acids to counteract endotoxin-stimulated metabolic dysregulation in porcine enterocytes.

ABSTRACT: Omega-3 polyunsaturated fatty acids (n-3 PUFA), such as the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are reported to beneficially affect the intestinal immunity. The biological pathways modulated by n-3 PUFA during an infection, at the level of intestinal epithelial barrier remain elusive. To address this gap, we investigated the proteomic changes induced by n-3 PUFA in porcine enterocyte cell line (IPEC-J2), in the presence and absence of lipopolysaccharide (LPS) stress conditions using shotgun proteomics analysis integrated with RNA-sequencing technology. A total of 33, 85, and 88 differentially abundant proteins (DAPs) were identified in cells exposed to n-3 PUFA (DHA:EPA), LPS, and n-3 PUFA treatment followed by LPS stimulation, respectively. Functional annotation and pathway analysis of DAPs revealed the modulation of central carbon metabolism, including the glycolysis/gluconeogenesis, pentose phosphate pathway, and oxidative phosphorylation processes. Specifically, LPS caused metabolic dysregulation in enterocytes, which was abated upon prior treatment with n-3 PUFA. Besides, n-3 PUFA supplementation facilitated enterocyte development and lipid homeostasis. Altogether, this work for the first time comprehensively described the biological pathways regulated by n-3 PUFA in enterocytes, particularly during endotoxin-stimulated metabolic dysregulation. Additionally, this study may provide nutritional biomarkers in monitoring the intestinal health of human and animals on n-3 PUFA-based diets.

SUBMITTER: Sundaram TS

PROVIDER: S-EPMC10703801 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Comprehensive proteomic analysis reveals omega-3 fatty acids to counteract endotoxin-stimulated metabolic dysregulation in porcine enterocytes.

Sundaram Tamil Selvi TS Addis Maria Filippa MF Giromini Carlotta C Rebucci Raffaella R Pisanu Salvatore S Pagnozzi Daniela D Baldi Antonella A

Scientific reports 20231207 1

Omega-3 polyunsaturated fatty acids (n-3 PUFA), such as the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are reported to beneficially affect the intestinal immunity. The biological pathways modulated by n-3 PUFA during an infection, at the level of intestinal epithelial barrier remain elusive. To address this gap, we investigated the proteomic changes induced by n-3 PUFA in porcine enterocyte cell line (IPEC-J2), in the presence and absence of lipopolysaccharide (LPS) stress condi ...[more]

PMID: 38062040

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Project description:Alcohol use disorder (AUD) patients comorbid with hepatitis C virus (HCV) infection (HCV + AUD) could have progressively severe clinical sequels of liver injury and inflammation. Serum zinc and several polyunsaturated fatty acids (PUFAs) get dysregulated in AUD as well as HCV. However, the extent of dysregulation of PUFAs and zinc deficiency and their interaction in HCV + AUD as a comorbid pathology has not been studied. We examined the role of dysregulation of FAs and low zinc in HCV + AUD patients. 138 male and female participants aged 21-67 years were grouped as HCV-only (Gr. 1; n = 13), HCV + AUD (Gr. 2; n = 25), AUD without liver injury (Gr. 3; n = 37), AUD with liver injury (Gr. 4; n = 51), and healthy volunteers (Gr. 5 or HV; n = 12). Drinking history, individual demographic measures, fasting fatty acids, liver function, and zinc were measured and analyzed. HCV + AUD patients showed the highest ALT level compared to the rest of the groups. Serum zinc concentrations were the lowest, and the proinflammatory shift was the highest (characterized by ω6 : ω3 ratio) in the HCV + AUD patients. Total ω3, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA5,3) were the lowest in HCV + AUD patients. Total ω3, α-linoleic acid (α-LA) along with covariable number of drinking days past 90 days (NDD90), eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA5,3) independently showed significant association with low zinc in the HCV + AUD patients. Heavy drinking pattern showed that NDD90 has a significant mediating role in the representation of the relationship between candidate ω3 PUFAs and zinc uniquely in the HCV + AUD patients. Low serum zinc showed a distinctively stronger association with total and candidate ω3s in the HCV + AUD patients compared to the patients with HCV or AUD alone, supporting dual mechanism involved in the exacerbation of the proinflammatory response in this comorbid cohort. This trial is registered with NCT#00001673.

Dataset Information

Comprehensive proteomic analysis reveals omega-3 fatty acids to counteract endotoxin-stimulated metabolic dysregulation in porcine enterocytes.

Publications

Comprehensive proteomic analysis reveals omega-3 fatty acids to counteract endotoxin-stimulated metabolic dysregulation in porcine enterocytes.

Similar Datasets

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