Endocrine and nutritional factors promoting WAT to BAT conversion

The process of white adipose tissue (WAT) browning has become a key focus topic in adipobiology research, due to its fat burning potential in obesity treatment. The interest in brown adipose tissue (BAT) derives from its unique ability to generate heat by adaptive thermogenesis. This process mediates the catabolism of energy substrates without the generation of ATP. Therefore, energy dissipation by BAT can control obesity by leading excess fat towards heat production. While brown adipocytes are rich in mitochondria and small lipid droplets (multilocular adipocytes), white adipocytes have few mitochondria and a single large lipid droplet (unilocular adipocytes). Moreover, uncoupling protein 1, the main driver of thermogenesis, is present only on the inner mitochondrial membrane of brown adipocytes, where it uncouples the oxidative phosphorylation from ATP synthesis. The research presented in this doctoral thesis involves the administration of endogenous and nutritional compounds to in vitro adipocyte models to evaluate their potential in inducing WAT browning. The chosen compounds are two myokines (b-aminoisobutyric acid and brain-derived neurotrophic factor) and two nutritional molecules (capsaicin and cis-9 retinoic acid). The effectiveness and the long-term effects of these biocompounds were here investigated in terms of lipid droplets and mitochondria structural changes on different cellular models. The results hereby discussed confirmed the potential of these bioactive compounds in inducing WAT browning, in agreement with previous knowledge and bringing new insights in this research field. Novel observations concerning doses and time-dependent effects of these browning factors could direct future research towards a correct and effective implementation of anti-obesity therapies.