Aging in Male Wistar Rats Associates With Changes in Intestinal Microbiota, Gut Structure, and Cholecystokinin-Mediated Gut–Brain Axis Function
Autor: | F. Escrivá, Luis G. Guijarro, David Álvarez-Cilleros, Patricia Sanmartín-Salinas, Carmen Álvarez, M Val Toledo-Lobo, Paula Pérez-Pardo, José M. Carrascosa, Ángela M. Valverde, Esther Lizárraga, María Fernández-Lobato, Carmen Rubio |
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Přispěvatelé: | Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (España), Comunidad de Madrid, Banco Santander, Fundación Ramón Areces |
Rok vydání: | 2020 |
Předmět: |
Lipopolysaccharides
Male Aging medicine.medical_specialty Gut–brain axis Inflammation Gut flora Diet High-Fat Systemic inflammation Adherens junction RNA Ribosomal 16S Internal medicine Brain-Gut Axis medicine Animals Obesity Gut bacteria Rats Wistar Adiposity Cholecystokinin Tight junction biology Leptin Mucins biology.organism_classification Satiety Gastrointestinal Microbiome Rats Endocrinology Mucin Geriatrics and Gerontology medicine.symptom |
Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
ISSN: | 1758-535X 1079-5006 |
Popis: | Aging in mammals is characterized by failure of the homeostatic mechanisms that regulate energy balance. Several mechanisms have been proposed such as the presence of a low-grade chronic inflammation in different tissues, as well as leptin and insulin resistance, but the primary alteration is not fully elucidated. The gut microbiota has recently emerged as a key player in a variety of metabolic and neurological disorders. A main concept in this context is the gut–brain axis that refers to alterations in the gut that mediate effects in the central nervous system, including those related with the control of energy balance. Using 16S rRNA analysis, we demonstrate that aged male Wistar rats have increased presence of mucin-degrading and lipopolysaccharide (LPS)-producing bacteria. In addition, old animals exhibit a lower number of neutral mucin secreting goblet cells, and a decrease of tight junctions and adherens junctions marker proteins, zonula occludens protein-1 (ZO-1) and β-catenin, respectively. These data are compatible with a thinner mucus layer and a weaker gut barrier in older animals that likely facilitate LPS leakage. Our data also show that cholecystokinin (CCK) satiating effect is impaired in aged rats, one of the expected effects of increased LPS leakage. In contrast, no overt signs of gut or systemic inflammation are observed. Changes in microbiota in old male Wistar rats present features of situations of increased adiposity, but different from those of obese animals. These could partly explain the increased adiposity and fat deposition in liver and heart as observed here. Spanish Government (grants BFU2008-04901-C03-01/BFI to J.M.C., BIO2016-76601-C3-2-R to M.F.-L., and RTI2018-094052-B-100 [MCI/AEI/FEDER, UE to A.M.V.] and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas (Instituto de Salud Carlos III) and Comunidad de Madrid, Spain (grants S2010/BMD-2423 to J.M.C., F.E., L.G.G., and A.M.V. and S2017/BMD-3684 to F.E. and A.M.V.). C.R. was supported by a predoctoral aid from Spanish Government. The Centro de Biología Molecular is recipient of institutional aids from Banco de Santander and Ramón Areces Foundation. |
Databáze: | OpenAIRE |
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