EFFECTS OF CAFETERIA DIET ON THE EXPRESSION OF NEUROSTEROIDOGENIC ENZYMES IN HYPOTHALAMIC NUCLEI INVOLVED IN THE CONTROL OF FOOD INTAKE.

LAZZARINO, GISELA P; ACUTAIN, M. FLORENCIA; ANDREOLI, M. FLORENCIA; STOKER, CORA; RAMOS, JORGE G

Workshop; 3rd Latin American International Workshop in Neuroendocrinology (IWNE 2015); 2015

EFFECTS OF CAFETERIA DIET ON THE EXPRESSION OF NEUROSTEROIDOGENICENZYMES IN HYPOTHALAMIC NUCLEI INVOLVED IN THE CONTROL OF FOOD INTAKE. Authors:Lazzarino, Gisela P.; Acutain, M. Florencia; Rosetti, M. Florencia; Andreoli,M. Florencia; Stoker, Cora; Ramos, Jorge G.Affiliations:Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica yCiencias Biológicas, Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral (ISAL),Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral- CONICET. Objectives: Cafeteria diet (CAF) is rich in highlypalatable, energy dense foods that are prevalent in Western society. It inducesslight obesity and increases energy intake through a neuropeptide mediated orexigenic signal of ventromedial (VMN) and paraventricular (PVN) nuclei. Steroids have a close relationship with the regulationof food intake: estradiol exerts an anorexigenic effect, whereas the administrationof progestagens such as progesterone and allopregnanolone has the oppositeeffect. Little is known about the steroidogenic pathway inhypothalamus, especially in discrete nuclei and its role in food intake controlremains unknown. Therefore, our aim was to determine the effects of cafeteriafeeding on expression of steroidogenic enzymes and steroid receptors in threedifferent hypothalamic nuclei involved in the control of food intake: arcuate nucleus (ARC), VMNand PVN. We also want to further study the relationship between energy intakeand neurosteroids synthesis.Methods and Results: Female Wistar rats were fed with a control or CAF dietfor 20 weeks since weaning. Animals were sacrificed, brains were extracted, sectioned into 300 µm slices and ARC, VMN and PVN weredissected using a 1 mmmicro punch needle. Total RNA was isolated, reverse transcribed and amplifiedby real time quantitative PCR to assess levels of expression of steroidogenicenzymes [cytochrome P450 side chain cleavage (P450scc), 3β-hydroxysteroiddehydrogenase (3β-HSD), cytochrome P450 17α-hydroxylase (P450-17α),P450aromatase (ARO) and 5α-reductase-1 (5aR)] and receptors [estrogenreceptor alpha (ERa) and progesterone receptor (PR)] in the extracted nuclei. InARC nucleus ERa andPR expression were increased by CAF diet (p<0.01) while 3β-HSD, ARO and 5aR remained unchanged. In VMN nucleus ERa, ARO and 3β-HSD showed an increment (p<0.001, p<0.01 and p<0.05,respectively) while PR and 5aR didnot present changes. In PVN nucleus 5aR was reduced(p<0.05), ARO expression rose(p<0.05) and 3β-HSD, ERa and PR did not change. P450scc and P450-17α expressionwas not detectable in any nucleus.Conclusions: Cafeteria diet induced differential expression ofsteroidogenic enzymes andsteroid receptors in differentnuclei implicated in food intake control. This could be related to their differential role intheregulationof appetite. ARO expression was doubled in PVN andVMN, which could lead to higher aromatization of testosterone into estradiol,representing an anorectic response that could compensate the orexigenic signalof neuropeptides in these nuclei. Financial Support: UniversidadNacional del Litoral and Argentine National Agency for the Promotion of Scienceand Technology (ANPCyT)