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Colonic dysmotility and inflammation associated with high fat diet-induced obesity: role of the enteric glia
- Matteo Fornai, Carolina Pellegrini, Vanessa D'Antongiovanni, Laura Benvenuti, Nunzia Bernardini, Chiara Ippolito, Cristina Segnani, Rocchina Colucci, Renè van den Wijngaard, Corrado Blandizzi, Luca Antonioli
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- Journal:
- Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
- Published online by Cambridge University Press:
- 10 June 2020, E494
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- Article
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Introduction
Enteric glial cells (EGCs) contribute to the regulation of bowel motility, and have been implicated in the onset and development of several digestive disorders. However, the involvement of EGCs in obesity-related intestinal dysmotility is unknown. Accordingly, this study examined the role of EGCs in colonic neuromuscular dysfunctions in a mouse model of diet-induced obesity.
Materials and MethodsC57BL/6 male mice (n = 6 per group) were fed with standard diet (SD) or high fat diet (HFD) for 8 weeks. Body and epididymal fat weight, and blood fasting glucose levels were evaluated the day before sacrifice. Colonic longitudinal muscle strips were set up in organ baths with Krebs solution and connected to isometric transducers. The effects of fluorocitrate (FC, gliotoxin) were tested on contractile responses mediated by NK1 tachykininergic receptors upon application of electrical stimuli (0.5 ms, 28 V, 10 Hz) [incubation with atropine, guanethidine, L-NAME, GR159897 and SB218795 (NK2 and NK3 antagonists, respectively)] or exogenous substance P (SP). Colonic levels of interleukin (IL)-1β, IL-6, malondialdehyde (MDA) and occludin (a tight junction protein involved the maintenance of mucosal barrier) were measured. Cultured rat EGCs were exposed to palmitate and lipopolysaccharide (LPS), either alone or in combination, to mimic the exposure to HFD. IL-1β and SP levels were then assessed in cell supernatants, while toll-like receptor 4 (TLR4) expression was evaluated in cell lysates.
ResultsHFD-mice displayed increments of body weight, epididymal fat weight and blood glucose levels. In in vitro experiments, electrically induced colonic tachykininergic contractions were enhanced in HFD mice, as compared with SD animals. No differences were observed when comparing contractions to exogenous SP. The increase in electrically evoked tachykininergic contractions was blunted upon incubation with the gliotoxin FC. Exogenous SP-induced contractions were not affected by FC. HFD mice displayed an increase in colonic IL-1β, IL-6 and MDA levels and a reduced occludin expression, as compared with SD mice. Exposure of EGCs to palmitate, alone or in combination with LPS, resulted in a significant increase in TLR4 expression, while LPS alone was without effects. The combination of palmitate and LPS increased significantly IL-1β and SP levels in cell supernatants, while single treatments were without effects.
DiscussionHFD is characterized by colonic dysmotility along with bowel inflammation, oxidative stress, and an impairment of mucosal barrier integrity. In this setting, the hyperactivation of EGCs, likely via TLR4, appears to contribute to inflammation and colonic tachykininergic motor dysfunctions.
Unravelling basin shoulder dynamics through detrital apatite fission-track signature: the case of the Quaternary Mugello Basin, Italy
- MARIA LAURA BALESTRIERI, MARCO BENVENUTI, RITA CATANZARITI
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- Journal:
- Geological Magazine / Volume 155 / Issue 7 / October 2018
- Published online by Cambridge University Press:
- 13 March 2017, pp. 1413-1426
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Detrital apatite fission-track (AFT) thermochronology has been applied to lower Pleistocene lacustrine fan-delta sediments of the NE shoulder of the Mugello Basin, the youngest and closest to the main watershed among the Northern Apennines intermontane basins. The aim was to decode the shoulder uplift dynamics during the development of the basin through the analysis of the Quaternary fluvio-lacustrine deposits. Bedrock shoulder analysis, performed to match the detrital AFT data with their source, revealed the presence of a unexpected only partially annealed portion of a turbidite foredeep unit (AFT ages >7–5 Ma) belonging to the structural complex that constitutes the shoulder bedrock. These data disagree with the AFT age distribution pattern of the well-studied Northern Apennines chain, suggesting a segmentation of the foredeep basin. The latter may have been related to the presence of a tectonically induced topographic high (pre-late Langhian) in the area limiting the thickness of the overriding Ligurian lid. On the other hand, detrital AFT data provided arguments for understanding the dynamics of Mugello Basin shoulder uplift and rotation. The proportion in the different stratigraphic units of the fan-delta sediments of single grains showing young (reset) and old (non-reset) ages points to late Early Pleistocene timing of the development of the SW-verging backthrust that characterizes the study area. These data confirm and detail the picture of an early Quaternary development of the Mugello Basin under a compressional setting, only later (middle Pleistocene to present) superimposed by normal faultings.
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