Browsing by Author "Vieira, Pedro"
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- Effect of blueberry supplementation on a diet-induced rat model of prediabetes—focus on hepatic lipid deposition, endoplasmic stress response and autophagyPublication . Ferreira, Gonçalo; Vieira, Pedro; Alves, André; Nunes, Sara; Preguiça, Inês; Martins-Marques, Tânia; Ribeiro, Tânia; Girão, Henrique; Figueirinha, Artur; Salgueiro, Lígia; Pintado, Manuela; Gomes, Pedro; Viana, Sofia; Reis, FlávioBlueberries, red fruits enriched in polyphenols and fibers, are envisaged as a promising nutraceutical intervention in a plethora of metabolic diseases. Prediabetes, an intermediate state between normal glucose tolerance and type 2 diabetes, fuels the development of complications, including hepatic steatosis. In previous work, we have demonstrated that blueberry juice (BJ) supplementation benefits glycemic control and lipid profile, which was accompanied by an amelioration of hepatic mitochondrial bioenergetics. The purpose of this study is to clarify the impact of long-term BJ nutraceutical intervention on cellular mechanisms that govern hepatic lipid homeostasis, namely autophagy and endoplasmic reticulum (ER) stress, in a rat model of prediabetes. Two groups of male Wistar rats, 8-weeks old, were fed a prediabetes-inducing high-fat diet (HFD) and one group was fed a control diet (CD). From the timepoint where the prediabetic phenotype was achieved (week 16) until the end of the study (week 24), one of the HFD-fed groups was daily orally supplemented with 25 g/kg body weight (BW) of BJ (HFD + BJ). BW, caloric intake, glucose tolerance and insulin sensitivity were monitored throughout the study. The serum and hepatic lipid contents were quantified. Liver and interscapular brown and epidydimal white adipose tissue depots (iBAT and eWAT) were collected for histological analysis and to assess thermogenesis, ER stress and autophagy markers. The gut microbiota composition and the short-chain fatty acids (SCFAs) content were determined in colon fecal samples. BJ supplementation positively impacted glycemic control but was unable to prevent obesity and adiposity. BJ-treated animals presented a reduction in fecal SCFAs, increased markers of arrested iBAT thermogenesis and energy expenditure, together with an aggravation of HFD-induced lipotoxicity and hepatic steatosis, which were accompanied by the inhibition of autophagy and ER stress responses in the liver. In conclusion, despite the improvement of glucose tolerance, BJ supplementation promoted a major impact on lipid management mechanisms at liver and AT levels in prediabetic animals, which might affect disease course.
- Intestinal mucosal alterations parallel central demyelination and remyelination: insights into the gut-brain axis in the cuprizone model of multiple sclerosisPublication . Ferreira, Carolina; Carvalho, Filipa; Vieira, Pedro; Alves, André; Palavra, Filipe; Almeida, Jani; Alves, Vera; Coscueta, Ezequiel; Pereira, Patrícia Dias; Pintado, Manuela; Sá, Helena; Castelo-Branco, Miguel; Reis, Flávio; Viana, SofiaBackground: The gut-brain axis has been increasingly recognized as a critical factor in Multiple Sclerosis (MS) pathophysiology. While its role in demyelination is well documented, gut-brain axis involvement during remyelination remains largely unexplored. Methods: Using the cuprizone (CPZ) model, which induces reversible demyelination and spontaneous remyelination upon toxin withdrawal, we investigated gut and brain changes during both disease stages in C57BL/6 mice. Animals were administered 0.2% cuprizone for 5 weeks to induce demyelination, followed by a 2-week recovery phase. Intestinal changes were evaluated through 1) gut microbiota profiling and metabolite production (short-chain fatty acids (SCFAs), indoxyl sulfate), 2) structural and barrier integrity via histology, mucus staining, and tight junction markers (ZO-1, occludin, claudin-5), 3) mucosal immunity through M1/M2 macrophage profiling and Th17/Treg ratios, and 4) expression of inflammatory and oxidative stress markers. Differences in brain demyelination/remyelination, gliosis and related molecular changes were determined using immunohistochemistry and real-time polymerase chain reaction (RT-PCR). Results: The demyelination peak was characterized by reduced abundance of SCFA-producing genus Akkermansia and Dubosiella, increased intestinal permeability at the level of the mucus layer and tight junction networks, and shifts in mucosal immunity toward a pro-inflammatory state characterized by M1 macrophages and Th17 cell expansion together with elevated levels of inflammatory cytokines (IL-17, IL-1?) and changes in oxidative stress-related enzymes (iNOS, HO-1, SOD1/2), all of which were partially reversed during the remyelination phase. Centrally, cuprizone-induced demyelination/remyelination and gliosis showed region-specific patterns. Neuroinflammation peaked during demyelination (TNF-?, IL-1?, IL-6, IL-17) and only partially resolved, suggesting that a balanced inflammatory response may aid remyelination. Conclusion: Our findings reveal that cuprizone-induced intestinal dysfunctions temporally parallel central nervous system (CNS) lesion dynamics, disclosing temporal coordination of both compartments and highlighting gut-brain axis impact on both disease stages.