DAILY VARIATION OF METABOLIC PARAMETERS ARE MODIFIED IN AN EXPERIMENTAL MODEL OF NUTRITIONAL OBESITY IN ADULT RATS

ALFONSO JO; SALINAS E; GUTIERREZ AGÜERO A; LOPEZ M; DELGADO SM; PEREZ CHACA V; CIMINARI E; BIAGGIO, V.; GOMEZ N; NAVIGATORE FONZO LS; ANZULOVICH AC

MENDOZA

Congreso; SBCuyo 2022; 2022

It is well known that the cause of obesity (OB) is multifactorial, including genetic, environmental, and dietary factors,among which, high-calorie diets play a central role in the development of the disease. On the other hand, severalinvestigations have related altered metabolic homeostasis and circadian parameters with Alzheimer disease. As part ofthe IMIBIO-SL institutional project (P-UE 013), which studies OB as a predisposing disease to the development ofchronic age-associated diseases and the search for early biomarkers with predictive potential, we obtained a nutritionalmodel of OB in adult rats and analyze potential early biomarkers of Alzheimer disease (AD). In this framework, ourobjective here was to evaluate the daily variation of metabolic parameters in our model of OB in adult rats. For this, maleWistar rats were weaned at 21 days of age, and fed a normocaloric diet (NC), containing 366 kcal of lipids/kg diet, then,at the 2-mo-age, they were randomly separated, and fed: one group, with the NC diet (control, CO, group) and the other,with a high-fat diet (HFD, 1570.7 kcal of margarine/kg diet, OB group), for the next 14 weeks. The animals were keptunder 12 h-light:12 h-dark and 22 24°C conditions, with water and food ad libitum. For chronobiological studies, at leastfour (4) animals from each group were euthanized every six (6) hours, at the zeitgeber times (ZT): ZT2, ZT8, ZT14, andZT20. All the experiments were performed following national and international guides for the care and use of laboratoryanimals and were approved by the CICUA (UNSL). Metabolic parameters such as glucose (G), triglycerides (TG), totalcholesterol (TC), HDLc, and LDLc + VLDLc levels, were determined in the serum of both CO and OB groups, usingcommercial kits. Statistical differences throughout the 24-h period were analyzed by one-way ANOVA, followed by apost-hoc test, to confirm statistical differences between ZTs within each group; chronobiological statistics were used to, and amplitude)between groups. We found G, HDLc, and TG levels vary significantly and rhythmically throughout a day in the serumof theLDLc+VLDLc do not display a rhythmic variation throughout a 24-h period. Noteworthy, the HFD abolished therhythmic patterns of daily G and TG levels and induced oscillating patterns of TC and LDLc+VLDLc levels, with thedaily means of G, TG, and LDLc+VLDLc levels increased in the OB group (P < 0.05, P < 0.01, and P < 0.05,respectively), while HDLc mesor decreased (P < 0.01). Most of the changes observed in circulating G, TC, andlipoproteins have been linked to the pathogenesis of AD, thus, our results would highlight potential early chronobiologicaland metabolic biomarkers for AD in an experimental model of OB in adult rats.