Early Exposure to a High-Fat Diet has more Drastic Consequences on Metabolism Compared with Exposure During Adulthood in Rats

Abstract

The aim of this study was determine whether the introduction of a high-fat diet during the peripubertal phase induces significant changes in body weight control, glucose homeostasis and the parasympathetic tonus compared with the administration of this diet to adult rats. High-fat diet was offered to male Wistar rats at weaning or during adulthood. A group of rats received high-fat diet for 60 days, from weaning to 81-day-old (HF81) or from 60 to 120-day-old (HF120), whereas 2 other groups received a normal-fat diet (i. e., NF81 and NF120). We analyzed adiposity, glucose homeostasis, insulin sensitivity, and vagal nerve activity. High-fat diet increased the accumulation of adipose tissue in all of the rats, but the difference was greater in the rats that were fed the high-fat diet since weaning (p<0.001). The HF rats showed glucose intolerance with high levels of insulin secretion during the glucose tolerance test (p<0.01). Rats that were fed the high-fat diet presented severe insulin resistance, indicated by a low K itt (p<0.01). Interestingly, the HF81 rats exhibited greater insulin resistance compared with the HF120 rats (p<0.05). The recordings of vagus nerve activity showed that the HF rats had higher parasympathetic activity than the NF rats irrespective of age (p<0.01). Our results show that a high-fat diet offered to rats just after weaning or in adulthood both cause impairment of glycemic homeostasis and imbalance in parasympathetic activity. Importantly, the consumption of high-fat diet immediately after weaning has more drastic consequences compared with the consumption of the same diet during adulthood.

Moderate Exercise Restores Pancreatic Beta-Cell Function and Autonomic Nervous System Activity in Obese Rats Induced by High-Fat Diet

“…Rodrigues et al showed that obese animals given early over-nutrition display impaired insulin signaling with low IRS-1 and PI3K levels and, consequently, a decrease in insulin sensitivity [33]; these results confirm our findings from the ivGTT and ipITT tests. We showed that HFD-SED rats were resistant to insulin when compared to Control-SED animals, as has been observed in other studies [8,13]. The development of insulin resistance was inhibited by moderate exercise in the HFD-EXE group in contrast to the respective sedentary group (HFD-SED).…”

“…Recently, our group showed that HFD introduced during adolescence causes more drastic consequences in metabolism than when HFD was administered in adult rats [13]. As with gestation and/or lactation, adolescence is a very sensitive phase in brain development; and any injury during the peripubertal period might cause permanent changes in metabolism when the individual reaches adult life [32].…”

“…Control animals received a standard chow diet (Nuvital CR1; Nuvilab®, Colombo, Paraná, Brazil) with 4.3 kcal/g ad libitum . HFD-fed animals received a previously described hypercaloric diet (5.9 kcal/g) rich in saturated fat [13]. A standard of three animals per cage for all groups was set.…”

Early treatment with metformin induces resistance against tumor growth in adult rats

“…26 Our group has shown that a highfat or low-protein diet administered during adolescence induces more drastic consequences on metabolism than when these diets are administered only during adulthood. 27,28 Reduced tumor cell growth, in vivo, by tumor cell transplantation, or in vitro, in cancer cell lines, was observed both in short or chronic treatment with metformin. Moreover, the antitumor effects were attributed to a direct effect of the drug, due to its concentration in the blood or in the cell culture solution.…”

“…[8][9][10] The pathologic complete response rate to neoadjuvant chemotherapy in diabetic patients with breast cancer was higher in patients taking metformin than in patients who had not been treated. 4,11,12 Various strategies have been reported to prevent cancer and metabolic syndrome, such as exercise training, functional food and metformin treatment, by modulating metabolism. 13,14 These strategies may support the hypothesis that some agents, such as metformin, could display some direct or indirect action on metabolism to resist further deleterious effects of tumor cell growth.…”