Avaliação transgeracional dos efeitos da dieta hipercalórica sobre o metabolismo e cognição em ratos

Abstract

Obesity is a complex multifactorial disorder caused by genetic and epigenetic factors, among others. An adverse intrauterine environment with excess or scarcity of food may expose the fetus to the development of metabolic syndrome, diabetes, and cardiovascular disease in adults, and may be transgenerationally passed through epigenetic changes. Physical exercise is a non-medicated form of prevention and treatment of obesity, improving cardiorespiratory fitness and body composition, among other factors. This study evaluated whether the diet rich in sucrose and lipids given to females of the F0 generation throughout their life, including gestation and lactation, would affect anxiety levels and memory patterns transgenerationally and if physical exercise has protective effect on the same parameters. Rats of the F0 generation were divided into four groups: sedentary (CSed) and exercised (CEx) controls; Sedentary (DSed) and exercise diet (DEx). From 21 to 120 days of age, the animals performed physical training on a treadmill at moderate to high intensity, and the control animals received normocaloric diet and the diet animals received the high sugar / high fat (HS / HF) diet during the same period. Males and females of the F1 and F2 generation were distributed in equalgroupsl to the maternal generation to which they belonged; however, consumed the normocaloric chow and did not perform physical training. The food consumption of the animals and their body weight were monitored. At 80 days, oral glucose tolerance test (OGTT) was performed. At 90 days, all animals were submitted to tests, for evaluation of anxiety level(elevated plus-maze) working memory (30 sec) and long-term (24h) (inhibitory avoidance test). At 110 days, there was euthanasia and the biometric parameters were evaluated. The normocaloric diet and physical training performed by the F0 generation promoted a lower accumulation of fat in the offspring, male and female from F1 generation, compared to CSed1 (retroperitoneal fat: 37.7% in females and 27.6% in males, perigonadal fat 28.16%, in males). Differently from what happened in the F1generation, the males of the DSed2 group presented a higher accumulation of perigonadal fat, 19.4%, when compared to the group Csed2. Additionally, the protective effect of physical training in relation to the lower accumulation of retroperitoneal and perigonadal fats in the F2 generation occurred only in the DEx2 group and in the males, with a reduction of 21% and 26.8%, respectively, in relation to the DSed2 group. Females of the DSed groups of the F1 and F2 generations were not intolerant to glucose, however, there was a 11.2% reduction in the glycemia of the females of the DEx1 group when compared to the DSed1 group. In contrast to what happened in the first-generation females, males from the DSed1 group were intolerant to glucose, with an increase in blood glucose by 18.45% when compared to the CSed1 group. The group DEx1 and DEx2 had a reduction in blood glucose of 18.45% and 24.75% when compared to the DSed group. The HS / HF diet consumed by the F0 generation reduced the long-term memory of the females of the DSed2 group by 88.6% when compared to the CSed2 group. It also increased the anxiety levels of male F1 generation from the DSed1 group in relation to the CSed1 and DEx1 groups. The HS / HF diet increased the anxiety level of the F1 generation males and caused long-term memory injury in females of the F2 generation, in addition to increasing the glycemia of the first-generation diet group males and causing higher fat accumulation In the F2 generation. Physical training had a protective effect on offspring glycemia, reducing the adiposity of male and female F1 pups (control group). This effect was only maintained in the F2 generation in the male offspring of the diet group. The HS / HF diet consumed by females from weaning to lactation alters metabolism, memory and anxiety levels in the F1 and F2 generations, particularly among males. Physical training of moderate to intense intensity performed by the F0 generation protects the progeny.