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

Adiposity-based chronic disease (ABCD, obesity) development and severity are directly related to changes in adipose tissue composition and function. It is acknowledged that adipose-originated metabolic inflammation and altered adipokine dynamics are strongly associated with systemic inflammation, insulin resistance, and dyslipidaemia. Although intermittent energy restriction (IER) seems to be as effective as continuous energy restriction (CER) for weight loss, its impact on metabolic-inflammatory status is often disregarded. We compared the effects of a 12-week IER versus CER on cardiometabolic and inflammatory markers in adults with obesity [mean (standard deviation) body mass index: 35.4 (3.7) kg/m2 ]. Our findings suggested that IER, in comparison to CER, could be advantageous to reduce pro-inflammatory cytokines associated with obesity, and, consequently, improve insulin resistance, regardless of the amount of weight loss. Aiming at studying the contribution of adipose tissue dysfunction in predicting peripheral insulin resistance, we demonstrated that adiponectin/leptin ratio (AdipoQ/Lep) was significantly correlated with both morphological and functional adipose tissue characteristics, reinforcing its usefulness as a biomarker for assessing adipose tissue function. More importantly, AdipoQ/Lep, triacylglycerols, and waist-to-hip ratio explained almost half of HOMA-IR (a surrogate marker of insulin resistance) variance, supporting that adipose tissue dysfunction appears to be a central feature of the pathophysiology of obesity and insulin resistance. Furthermore, adipose tissue and metabolic dysfunction may be exacerbated by exposure to mixtures of lipophilic persistent organic pollutants (POPs) that are stored in lipid droplets of adipocytes. This led us to characterize the levels of POPs in plasma and evaluate their putative effects on weight loss and cardiometabolic and inflammatory markers in adults with obesity undergoing a dietary intervention for weight loss. Twelve different POPs, mainly organochlorine pesticides, were determined by gas chromatography with electron-capture detection. Persistent organic pollutants are pervasive in this population and their concentration in plasma seems to be associated with obesity-related characteristics. Despite the pre-intervention POPs levels in plasma did not appear to have an impact on weight loss and changes in metabolic parameters, our findings revealed an association between POPs levels and inflammatory cytokines that should be further investigated. A comprehensive understanding of these results allows us to provide novel insights with public health and clinical significance relating to obesity management, adipose tissue and metabolism dysfunction, and emergent environmental risk factors for metabolic diseases. Our findings highlight the prominent role of adipose tissue function and adipose tissue-derived factors on obesity-associated metabolic complications as well as support that the focus of obesity management could be moved towards improving patient-centred metabolic-inflammatory outcomes rather than weight loss alone