Fat metabolism and the control of food intake

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Obesity and overweight are rising at alarming rates globally, driven by an environment that encourages sedentary behavior and overconsumption. Research indicates that dietary fat significantly contributes to overfeeding and obesity, making it crucial to understand the physiological mechanisms regulating food intake, particularly those linked to fat metabolism. This thesis aims to enhance our understanding of fatty acid oxidation (FAO) in food intake control. Evidence suggests that peripheral FAO plays a role in metabolic feeding regulation, as peripheral administration of FAO inhibitors has been shown to stimulate feeding across various species, including humans. However, despite the strong evidence for feeding stimulation from reduced FAO, there is a lack of data supporting the idea that increased FAO inhibits feeding. Thus, this thesis specifically investigates the feeding-inhibitory effects of enhanced FAO by testing its role when fatty acid supply from endogenous fat stores is increased. This was accomplished pharmacologically with specific β3-adrenergic receptor agonists and physiologically through pre-test food deprivation. The impact of FAO on feeding responses was assessed using the FAO inhibitor mercaptoacetate and by disrupting potential neural mediation through subdiaphragmatic vagal deafferentation.