Publicação
Preclinical impact of blueberry supplementation in healthy and prediabetic conditions - Focus on gut microbiota and hepatic mitochondria bioenergetics
| Resumo: | Prediabetes, recognized as a state of high risk for the development of type 2 diabetes mellitus (T2DM) and related complications, is certainly a privileged phase to implement strategies to prevent or delay the disease progression to more advanced stages. Unhealthy lifestyles, marked by sedentarism and unbalanced dietary habits, are important contributors to the growing incidence of various metabolic disorders, namely prediabetes. Several recent evidence point towards unbalanced diets, including the hypercaloric ones, as major drivers of gut microbiota (GM) dysbiosis, which may be involved in the onset of metabolic deregulation. Although the putative engagement of dysbiosis as early as prediabetes remains to be elucidated, the adoption of healthier dietary regimens as a first-line therapy is now well established. During the recent years, we have witnessed a change in consumers´ attitude towards the adoption of healthier dietary patterns to avoid the onset of certain diseases while ensuring a better life quality. Thus, the demand and consumption of functional foods and natural supplements rich in phytochemicals, namely polyphenols, are a contemporary trend. Still, high doses of phenolic compounds have already been associated with adverse effects, namely at the hepatic level, a controversial issue within the scientific community that warrants further studies. Blueberry (BB) fruit has become popular, both to be consumed as a food or as a supplement, by virtue of their claimed health benefits (e.g. antioxidant, prebiotic), as they are a valuable source of bioactive compounds (i.e. polyphenols and fiber). Even so, the effective consequences of its excessive intake in a healthy condition are yet to be defined. Likewise, a lack of consistent evidence subsists regarding the expected positive impact of a BB-derived nutraceutical intervention in a prediabetic condition, presumed on the basis of its panoply of health-related properties in several metabolic diseases, including in T2DM. Considering these rationales, the main aims of this thesis were the evaluation of the effects arising from a long-term BB supplementation, in healthy and prediabetic conditions, with particular focus on GM and liver tissue. BB was administered in the juice form, in a dose of 25 g/Kg of body weight for 14 weeks in two experimental conditions: a) in healthy Wistar rats and b) in a hypercaloric diet- induced prediabetic rat model. When a healthy condition was foreseen, our observations corroborated the expected increase in antioxidant activity BB-driven, accompanied by an unchanged metabolic profile. Somewhat surprisingly, no profound changes were observed in the composition and function of the microbial community. In the liver, BB supplementation elicited a scenario of mitochondrial adaptation without functional and structural changes in the hepatic tissue. Indeed, we found a marked remodeling of mitochondrial bioenergetics, accompanied by a reprogramming of metabolic transcriptomics and an expressive repression of inflammation-related genes. Collectively, these observations suggest the activation of an adaptive cellular response to an overload of the antioxidant cargo triggered by a prolonged consumption of BB. Regarding the impact of BB on prediabetes, we observed a prevention of hypercaloric diet-evoked metabolic changes. Apparently, this metabolic protection could not be explained by the impact on GM. Conversely, and paralleling an antioxidant effect, we observed a reduction in hepatic steatosis along with a clear improvement in hepatocyte mitochondrial bioenergetics, suggesting that mitochondria may be a key player in early disease progression. Moreover, BB consumption has positively modulated the hepatic gene expression of key targets involved in fatty acid oxidation, insulin signaling, inflammation, as well as the mitochondrial respiratory chain, all of which were found compromised in the liver of prediabetic rats. Collectively, these results advocate that the improvement of hepatic mitochondrial function may be a crucial mechanism by which BB exerts its protective effect in prediabetes. In conclusion, the results of this thesis suggest that the long-term supplementation of BB may be an effective nutraceutical intervention to avoid the progression of prediabetes; still, the marked impact on hepatic mitochondrial bioenergetics in a healthy condition raises the need of further studies for full clarification. |
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| Autores principais: | Nunes, Sara Raquel Ramalho Pereira |
| Assunto: | Blueberry long-term supplementation healthy condition prediabetes hypercaloric diet gut microbiota hepatic mitochondria bioenergetics |
| Ano: | 2022 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Coimbra |
| Idioma: | inglês |
| Origem: | Estudo Geral - Universidade de Coimbra |
| Resumo: | Prediabetes, recognized as a state of high risk for the development of type 2 diabetes mellitus (T2DM) and related complications, is certainly a privileged phase to implement strategies to prevent or delay the disease progression to more advanced stages. Unhealthy lifestyles, marked by sedentarism and unbalanced dietary habits, are important contributors to the growing incidence of various metabolic disorders, namely prediabetes. Several recent evidence point towards unbalanced diets, including the hypercaloric ones, as major drivers of gut microbiota (GM) dysbiosis, which may be involved in the onset of metabolic deregulation. Although the putative engagement of dysbiosis as early as prediabetes remains to be elucidated, the adoption of healthier dietary regimens as a first-line therapy is now well established. During the recent years, we have witnessed a change in consumers´ attitude towards the adoption of healthier dietary patterns to avoid the onset of certain diseases while ensuring a better life quality. Thus, the demand and consumption of functional foods and natural supplements rich in phytochemicals, namely polyphenols, are a contemporary trend. Still, high doses of phenolic compounds have already been associated with adverse effects, namely at the hepatic level, a controversial issue within the scientific community that warrants further studies. Blueberry (BB) fruit has become popular, both to be consumed as a food or as a supplement, by virtue of their claimed health benefits (e.g. antioxidant, prebiotic), as they are a valuable source of bioactive compounds (i.e. polyphenols and fiber). Even so, the effective consequences of its excessive intake in a healthy condition are yet to be defined. Likewise, a lack of consistent evidence subsists regarding the expected positive impact of a BB-derived nutraceutical intervention in a prediabetic condition, presumed on the basis of its panoply of health-related properties in several metabolic diseases, including in T2DM. Considering these rationales, the main aims of this thesis were the evaluation of the effects arising from a long-term BB supplementation, in healthy and prediabetic conditions, with particular focus on GM and liver tissue. BB was administered in the juice form, in a dose of 25 g/Kg of body weight for 14 weeks in two experimental conditions: a) in healthy Wistar rats and b) in a hypercaloric diet- induced prediabetic rat model. When a healthy condition was foreseen, our observations corroborated the expected increase in antioxidant activity BB-driven, accompanied by an unchanged metabolic profile. Somewhat surprisingly, no profound changes were observed in the composition and function of the microbial community. In the liver, BB supplementation elicited a scenario of mitochondrial adaptation without functional and structural changes in the hepatic tissue. Indeed, we found a marked remodeling of mitochondrial bioenergetics, accompanied by a reprogramming of metabolic transcriptomics and an expressive repression of inflammation-related genes. Collectively, these observations suggest the activation of an adaptive cellular response to an overload of the antioxidant cargo triggered by a prolonged consumption of BB. Regarding the impact of BB on prediabetes, we observed a prevention of hypercaloric diet-evoked metabolic changes. Apparently, this metabolic protection could not be explained by the impact on GM. Conversely, and paralleling an antioxidant effect, we observed a reduction in hepatic steatosis along with a clear improvement in hepatocyte mitochondrial bioenergetics, suggesting that mitochondria may be a key player in early disease progression. Moreover, BB consumption has positively modulated the hepatic gene expression of key targets involved in fatty acid oxidation, insulin signaling, inflammation, as well as the mitochondrial respiratory chain, all of which were found compromised in the liver of prediabetic rats. Collectively, these results advocate that the improvement of hepatic mitochondrial function may be a crucial mechanism by which BB exerts its protective effect in prediabetes. In conclusion, the results of this thesis suggest that the long-term supplementation of BB may be an effective nutraceutical intervention to avoid the progression of prediabetes; still, the marked impact on hepatic mitochondrial bioenergetics in a healthy condition raises the need of further studies for full clarification. |
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