(P13-005-25) Progression of Metabolic Alterations Associated With Adipose Tissue Dysfunction in Rats Fed With a High-Fat Diet and a Fructose Beverage

Objectives: Investigate the chronological effects of consuming a typical Mexican diet high in oxidized fats and fructose on AT and liver metabolism  in rats and their metabolic consequences.

Methods: Male Wistar rats were divided into 2 experimental groups: 1) control diet and tap water (C); and 2) high-oxidized fat diet (33% fat) and 15% fructose water (HFD+F). Body weight recording and oral glucose tolerance test (OGTT) were performed at 1.5, 3, 6, 12 and 18 weeks. In each time point, 5 rats per group were euthanized to collect AT and liver for histomorphological analysis and immunoblots and serum to determine biochemical parameters.

Results: Rats fed HFD+F did not increase body weight with respect to C, despite the high caloric density. From week 3, HFD+F rats developed significant AT hypertrophy along with increased fat content and inflammatory markers in the liver, resulting in higher circulating total and LDL cholesterol, as well as lower HDL cholesterol levels from week 1.5. By week 6, HFD+F rats showed altered fasting blood glucose, increased OGTT area under the curve, HOMA-IR, and triglycerides. At week 12, increased liver enzymes was observed.

Conclusions: The consumption of a HFD+F generates sequential metabolic alterations, beginning with the dysfunction of AT and excessive fat accumulation in the liver. This results in hepatic lipotoxicity and the disruption of lipid homeostasis, leading to hypercholesterolemia and, subsequently, hypertriglyceridemia accompanied by glucose metabolism abnormalities. Therefore, this diet, based on the unhealthy daily eating habits of many Mexicans, creates a model of normal-weight obesity, highlighting the need for more thorough metabolic studies than simply evaluating body weight or BMI to understand the health status of individuals.

Funding Sources: CONAHCYT (Convocatoria Ciencia de Frontera 2023, Project CF-2023-G-1292) and Sociedad Mexicana de Nutrición y Endocrinología, A. C. to JGJR