Dissertação de Mestrado Nutrição Humana e Metabolismo 2022 Faculdade de Ciências Médicas, Universidade NOVA de Lisboa

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.