Browsing by Author "Viana, Sofia"
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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.
- Exploring yeast glucans for vaccine enhancement: sustainable strategies for overcoming adjuvant challenges in a SARS-CoV-2 modelPublication . Azevedo-Silva, João; Amorim, Manuela; Tavares-Valente, Diana; Sousa, Pedro; Mohamath, Randolph; Voigt, Emily A.; Guderian, Jeffrey A.; Kinsey, Robert; Viana, Sofia; Reis, Flávio; Pintado, Manuela E.; Paddon, Christopher J.; Fox, Christopher B.; Fernandes, João C.Vaccine adjuvants are important for enhancing vaccine efficacy, and although aluminium salts (Alum) are the most used, their limited ability to induce specific immune responses has spurred the search for new adjuvants. However, many adjuvants fail during product development due to manufacturability, supply, stability, or safety concerns. This work hypothesizes that protein-free yeast glucans can be used as vaccine adjuvants due to their known immunostimulatory activity and high abundancy. Thus, high molecular weight glucans with over 99% purity, comprising 64–70% β-glucans and 29–35% α-glucans, were extracted from a wild-type yeast and an engineered yeast to produce a steviol glycoside. These glucans underwent carboxymethylation to enhance solubility. Both water-dispersible and particulate glucans were evaluated as adjuvants, either alone or in combination with Alum or squalene stable emulsion (SE), for a SARS-CoV-2 vaccine. The study demonstrated that glucans triggered a robust immune response and enhanced the effects of Alum and SE when used in combination, both in vitro and in vivo. Water-dispersible glucans combined with Alum, and particulate glucans combined with SE, increased the production of specific antibodies against SARS-CoV-2 spike protein and enhanced serum neutralization titers against SARS-CoV-2 pseudovirus. Furthermore, the results indicated that larger molecular weight glucans from engineered yeast exhibited stronger immunogenic activity in comparison to wild-type yeast glucans. In conclusion, appropriately formulated glucans have the potential to be scalable, low-cost vaccine adjuvants, potentially overcoming the limitations of current adjuvants.
- The use of cecal samples from Wistar rats in in vitro fermentation to determine the effect of Fish and Pomegranate oil in gut microbiota alterations induced by a Western dietPublication . Salsinha, Ana Sofia; Cima, André; Araújo-Rodrigues, Helena; Viana, Sofia; Reis, Flávio; Coscueta, Ezequiel R.; Rodríguez-Alcalá, Luis Miguel; Relvas, João B.; Pintado, ManuelaThe influence of gut microbiota in the onset and development of several metabolic diseases, such as obesity and diabetes, has gained attention over the last few years. Indeed, diet plays an essential role in gut microbiota modulation. Western diet (WD), characterized by high-sugar and high-fat consumption, alters gut microbiome composition, diversity index, microbial relative levels, and functional pathways. Several polyunsaturated fatty acids have been showing promising health effects, but their impact on gut microbiota is still overlooked. The effect of Fish oil (omega-3 source - EPA and DHA) and Pomegranate oil (punicic acid source), and a mixture of both oils in gut microbiota was determined by subjecting the oil samples to in vitro fecal fermentations using as fecal inoculum cecal samples from rats from two different dietary groups: control diet (CD) and high-fat high-sugar diet (WD). 16S amplicon metagenomics sequencing showed that Fish oil+Pomegranate oil from the WD group increased α-diversity. This sample can also increase the relative abundance of the Firmicutes and Bacteroidetes phylum as well as Akkermansia and Blautia, which were affected by the WD consumption. All samples were able to increase butyrate and acetate concentration in the WD group. Amino acids are precursors of important neuroactive molecules. Tyrosine concentrations, a precursor for dopamine and norepinephrine, increased in the Fish oil+Pomegranate oil WD sample. GABA, an important neurotransmitter, was also increased in WD samples. These results suggest a positive impact of these oils’ mixture on gut-brain axis modulation. It was demonstrated, for the first time, the great potential of using a mixture of both Fish and Pomegranate oil to restore the gut microbiota changes associated with WD consumption.