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intestinal epithelium is a principal site for environmental agents\u2019 detection. Several inflammation- and stress-related signalling pathways have been identified as key players in these processes. However, it is still unclear how the chronic intake of inadequate nutrients triggers inflammatory signalling pathways in different intestinal regions. We aimed to evaluate the impact of unhealthy dietary patterns, starting at a younger age, and the association with metabolic dysfunction, intestinal inflammatory response, and obesity in adulthood. A rat model was used to evaluate the effects of the consumption of sugary beverages (HSD) and a Western diet (WD), composed of ultra-processed foods. Both diets showed a positive correlation with adiposity index, but a positive correlation was found between the HSD diet and the levels of blood glucose and triglycerides, whereas the WD diet correlated positively with triglyceride levels. Moreover, a distinct inflammatory response was associated with either the WD or HSD diets. The WD induced an increase in TLR2, TLR4, and nuclear factor-kappa B (NF-\u03baB) intestinal gene expression, with higher levels in the colon and overexpression of the inducible nitric oxide synthase. In turn, the HSD diet induced activation of the TLR2-mediated NF-\u03baB signalling pathway in the small intestine. Altogether, these findings support the concept that early intake of unhealthy foods and nutrients are a main exogenous signal for disturbances of intestinal immune mechanisms and in a region-specific manner, ultimately leading to obesity-related disorders in later life.<\/jats:p>","DOI":"10.3390\/ijms231810984","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T21:47:27Z","timestamp":1663624047000},"page":"10984","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Unhealthy Diets Induce Distinct and Regional Effects on Intestinal Inflammatory Signalling Pathways and Long-Lasting Metabolic Dysfunction in Rats"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0621-4424","authenticated-orcid":false,"given":"Sofia","family":"Nogueira","sequence":"first","affiliation":[{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences, University Institute of Health Sciences, Advanced Polytechnic and University Cooperative (CESPU), CRL, 4585-116 Gandra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2236-1029","authenticated-orcid":false,"given":"Joana","family":"Barbosa","sequence":"additional","affiliation":[{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences, University Institute of Health Sciences, Advanced Polytechnic and University Cooperative (CESPU), CRL, 4585-116 Gandra, Portugal"},{"name":"UCIBIO, REQUIMTE\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7753-0219","authenticated-orcid":false,"given":"Juliana","family":"Faria","sequence":"additional","affiliation":[{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences, University Institute of Health Sciences, Advanced Polytechnic and University Cooperative (CESPU), CRL, 4585-116 Gandra, Portugal"},{"name":"UCIBIO, REQUIMTE\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5078-980X","authenticated-orcid":false,"given":"Susana I.","family":"S\u00e1","sequence":"additional","affiliation":[{"name":"CINTESIS@RISE, MEDCIDS, Faculty of Medicine, University of Porto, Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine of University of Porto, Al Prof Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2967-6990","authenticated-orcid":false,"given":"Armando","family":"Cardoso","sequence":"additional","affiliation":[{"name":"CINTESIS@RISE, MEDCIDS, Faculty of Medicine, University of Porto, Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine of University of Porto, Al Prof Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9157-5541","authenticated-orcid":false,"given":"Raquel","family":"Soares","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, Al Prof Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, R. 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