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MONET: Unravelling Microbiota-gut-brain axis paintings in obesity-associated Neuroinflammation: the blackbErry signaTure study
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The influence of anthocyanin treatment on the mesenteric adipose tissue expression of enampt in animal models of obesity
Publication . Projecto, Maria Margarida Nobre; Silvestre, Marta P.; Faria, Ana
Introduction: Nicotinamide Phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for NAD biosynthesis. Its extracellular form (eNAMPT), mainly secreted by visceral fat, has been shown to have bimodal, concentration- and structure-functional-dependent effects in important metabolic pathways and has been connected to a wide variety of diseases. Data suggests that as serum eNAMPT concentration rises to pathophysiological levels, as in obesity and type 2 diabetes (T2D), eNAMPT adopts a monomeric form capable of proinflammatory NAD-independent effects. Strategies to block the actions of the eNAMPT monomer could represent promising therapeutic approaches for obesity-related metabolic disorders. Consumption of anthocyanin rich foods appears to prevent or treat obesity-related consequences, such as T2D, inflammation and oxidative stress, but the mechanism behind this is unknown. Moreover, anthocyanins have been shown to inhibit the secretion of eNAMPT in animal models. With this study, we aim to understand if treating a rat model of obesity with anthocyanins could abrogate the impact of a high fat diet in the expression of monomeric eNAMPT. Methods: Mesenteric adipose tissue (mAT) was obtained from four groups of male Wistar rats, treated with different diets: (C) standard diet; (BE) standard diet + blackberry extract; (HFD) high fat diet; (HFDBE) high-fat diet + blackberry extract. eNAMPT monomer’s protein expression was measured by Western Blotting, after protein extraction and quantification from mAT, to access the differences between the animals fed a standard diet and those of increased metabolic risk – HFD, with and without treatment with anthocyanins. Results: The mAT from HFD rats displayed a higher expression of eNAMPT monomer, compared to C rats (138,6% ± 11,4% HFBE vs 100% C, p=0,01). The anthocyanin’s treatment influence on mAT eNAMPT monomer expression was also assessed. mAT eNAMPT monomer expression was significantly decreased in the HFDBE group compared to HFD (-54,1 ± 15,3 % [-89.4, -18.8], p<0,01). Conclusions: Anthocyanin consumption might be an interesting dietary approach to abrogate the impact of a high fat diet on the rise of monomeric eNAMPT in mesenteric adipose tissue. Ultimately, our results suggest that long-term anthocyanin treatment/supplementation might be effective for sustaining lower levels of monomeric eNAMPT in the context of diet-induced obesity, potentially preventing or delaying the consequent metabolic impairments such as the alarming epidemic of T2D.
Efeito de um extrato de amora em biomarcadores de esteatose hepática não-alcóolica num modelo de ratinho humanizado com obesidade
Publication . Nanque, Maristela Sependa Sá; Araújo, João Ricardo; Maria, Ana
Introdução: A esteatose hepática não alcoólica (EHNA) está intimamente associada à obesidade. Apesar do consumo de frutos vermelhos ricos em antocianinas, nomeadamente a amora, ter um efeito protetor no desenvolvimento e progressão da EHNA, e da obesidade a ela associada, os mecanismos moleculares subjacentes encontram-se ainda por explorar. Objetivo: Avaliar o impacto do consumo de um extrato de amora nos biomarcadores metabólicos de EHNA, num modelo de ratinho humanizado com obesidade induzida por disbiose e dieta rica em lípidos e sacarose. Material e métodos: Ratinhos machos C57BL/6J foram aleatoriamente distribuídos em 3 grupos (n=8 ratinhos/grupo): 1) grupo DH, ratinhos com obesidade induzida por dieta rica em lípidos e sacarose durante 5 semanas; 2) grupo DH+TMF, ratinhos com obesidade induzida simultaneamente por transplante fecal de microbiota proveniente de dadores obesos e dieta rica em lípidos e sacarose; e 3) grupo DH+TMF+AA, ratinhos com obesidade induzida simultaneamente por transplante de microbiota e dieta rica em lípidos e sacarose, aos quais foi administrado um extrato de amora. A concentração hepática e sérica de triacilgliceróis e glicerol livre, e a expressão hepática de proteínas chave da via de sinalização da insulina (Akt) e da síntese de ácidos gordos (carboxílase da acetil-coA), foram determinadas. Resultados: A concentração de triacilgliceróis e a expressão proteica da Akt, ambas a nível hepático, foram semelhantes nos 3 grupos. Contudo, a concentração plasmática de trialcilgliceróis diminuiu cerca de 25-35% no grupo DH+TMF+AA comparativamente aos grupos DH+TMF e DH, estando este efeito associado a um aumento, da mesma ordem de grandeza, da concentração plasmática de glicerol livre no grupo DH+TMF+AA. Relativamente à expressão hepática da carboxílase da acetil-coA, verificou-se um aumento, superior a 50%, no grupo DH+TMF+AA comparativamente aos grupos DH+TMF e DH. Conclusão: A nível hepático, o extrato de amora não altera nem a acumulação de triacilgliceróis nem a expressão de proteínas chave da via de sinalização da insulina em ratinhos humanizados com obesidade. Contudo, o extrato de amora é capaz de reduzir a concentração circulante de triacilgliceróis, levando a um aumento, eventualmente compensatório, da lipogénese hepática.
The impact of blackberry supplementation on skeletal muscle mitochondrial dynamics in a humanized mouse model of obesity
Publication . Rodrigues, Luís; Araújo, João Ricardo; Faria, Ana
Background: Obesity is a chronic and multifactorial metabolic disorder that substantially affects health and quality of life. At skeletal muscle level, obesity is associated with impaired mitochondrial dynamics, being unclear if this precedes and/or follows the disease development. Blackberry anthocyanins or proanthocyanidins attenuate metabolic alterations associated with obesity including the impairment of mitochondrial dynamics in the adipose tissue. However, their impact on the skeletal muscle mitochondrial dynamics during obesity has not yet been explored. Aim: In a humanized mouse model of obesity, evaluate the effect of a blackberry extract consumption on the expression of key proteins involved in mitochondrial dynamics of the skeletal muscle. Material and Methods: C57BL/6J male mice were randomly distributed into 3 groups (n=8 mice/group): (1) HFD group, mice with obesity induced by a high-fat high-sugar diet for 5 weeks; (2) HFD+FMT group, mice with obesity induced by faecal microbiota transplantation from obese donors and a high-fat high-sugar diet; and (3) HFD+FMT+BB group, mice with obesity induced by faecal microbiota transplantation and a high-fat high-sugar diet, and administered with a blackberry extract. Skeletal muscle expression of mitochondrial proteins of fusion (mitofusin 2), fission (dynamin-related protein 1), biogenesis (peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC-1α]) and mitophagy (Parkin) were determined by western blot. Results: The protein expression of mitofusin 2 and dynamin-related protein 1 increased, by 30-40%, in the skeletal muscle of mice from the HFD+FMT+BB group when compared with mice from both HFD+FMT and HFD groups. Although the expression of PGC-1α remained unaltered in the three groups of mice, the expression of Parkin was 30% higher in the skeletal muscle of mice from the HFD+FMT+BB group when compared with mice from the HFD+FMT group. Conclusion: Blackberry extract consumption seems to restore mitochondrial fusion, fission and mitophagy in the skeletal muscle of a humanized mouse model of obesity. This suggests a protective and therapeutic potential of blackberry against alterations in mitochondrial dynamics associated with obesity.
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Fundação para a Ciência e a Tecnologia
Programa de financiamento
3599-PPCDT
Número da atribuição
PTDC/BAA-AGR/7419/2020