CHARACTERIZATION OF A NEW NOTHOBRANCHIUS FURZERI MODEL OF A DIET-INDUCED OBESITY

The global epidemic of obesity is a major public health problem today. Due to augmented life expectancy, obesity is growing in prevalence among older people. Increasing efforts therefore need to be made to identify effective strategies able to promote healthy aging and curb the obesity pandemic [1]. The use of animal models to study the phenomena underlying obesity (genetic, physiological, epigenetic and environmental), as well as research on potential treatments, offers enormous potential. However, to understand the impact of ageing on obesity, it is primary to conduct studies on old animals, in order to phenocopy the systemic ageing context [2]. In the last few years, the African killifish Nothobranchius furzeri has emerged as an important model system for the study of vertebrate biology. N. furzeri is an annual fish that inhabits seasonal freshwater ponds in the southeast of Africa and is characterized by rapid growth and early sexual maturation. This fish, with a median lifespan of 3 and 7 months, is currently considered the shortest-lived vertebrate that can be bred in captivity. Importantly, despite its short lifespan, N. furzeri recapitulates typical age-dependent phenotypes and pathologies making this fish a suitable model for aging research [3]. The goal of our work is to establish and characterize a new model of diet-induced obesity (DIO). The research was approved with protocol 1141/2020-PR by the Ministry of Health. First objective is to define the dietary protocol to determine the obese phenotype. To this aim, 77 fishes belonging to MZM 04/10 strain, both male and female, at 6 weeks of age were divided into different group diets and fed for 14 weeks with increasing doses of Chironomus spp. as follows: a) 300mg/die (ctrl); b) 540mg/die; c) 660mg/die; d) 780mg/die. Every two weeks morphometric measurements, i.e. body weight and length, were individually taken to assess growth curves and define the body mass index. Morphological studies on whole trunk histological sections allowed us to a) analyze liver structure, b) measure the thickness of visceral and subcutaneous adipose tissue, c) characterize the complex carbohydrates. Two master-key lipogenic factors, namely PPARγ and SREBP-1, have also been tested on liver homogenates by means of Western blot. Our preliminary results indicate that the diet administered to group d is the most obesogenic. Our pilot study is the first step toward the analysis of obese phenotype during vertebrate ageing.