The prevalence of obesity is increasing at alarming rate worldwide. Obesity is a multifactorial disease generated by an alteration in balance between energy intake and expenditure, also dependent on genetic and non-genetic factors. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older
age groups. Both obesity and ageing are conditions leading to serious health problems, increasing risk for disease and death. In particular, ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and metabolic syndrome. Obesity in the elderly is thus a serious concern and new animal models are
required to help us understand the signaling pathways underlying this condition. Our research thus aims to established Nothobranchius furzeri as model of diet-induced obesity (DIO). The teleost African turquoise killifish N.furzeri is recently validated model organism for ageing research, being the vertebrate with the shortest lifespan ever described under laboratory conditions. Importantly, despite its short lifespan, this fish recapitulates typical age-dependent phenotypes and pathologies, displaying also a conserved response to environmental stimuli known to affect the ageing rate in other species. With this project we propose to develop a model of DIO by overfeeding with
high fat diet (HFD) animals (MZM strain) from 5 weeks post hatching (wph) (young-adult) until 27wph (onset of ageing-related features) and comparing to control killifish fed under physiological conditions. Then we intend to characterize this new established DIO model analyzing the major components of the gut-brain endocrine axis, the
gut microbiota (GM) composition and glycohistochemical profile changes and the effects of flavonoids as potential modulators of lipid-activated nuclear receptors (NRs). Our data will serve as a template for future functional studies to dissect the neuroendocrine regulators of energy homeostasis.