Early life stress interacts with the diet deficiency of omega-3 fatty acids during the life course increasing the metabolic vulnerability in adult rats

Abstract

Early stress can cause metabolic disorders in adulthood. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) deficiency has also been linked to the development of metabolic disorders. The aim of this study was to assess whether an early stressful event such as maternal separation interacts with the nutritional availability of n-3 PUFAs during the life course on metabolic aspects. Litters were randomized into: maternal separated (MS) and non-handled (NH). The MS group was removed from their dam for 3 hours per day and put in an incubator at 32 °C on days 1° to 10° postnatal (PND). On PND 35, males were subdivided into diets that were adequate or deficient in n-3 PUFAs, and this intervention was applied during the subsequent 15 weeks. Animal's body weight and food consumption were measured weekly, and at the end of the treatment tissues were collected. MS was associated with increased food intake (p = 0.047) and weight gain (p = 0.012), but no differences were found in the NPY hypothalamic content between the groups. MS rats had also increased deposition of abdominal fat (p<0.001) and plasma triglycerides (p = 0.018) when compared to the NH group. Interactions between early life stress and n-3 PUFAs deficiency were found in plasma insulin (p = 0.033), HOMA index (p = 0.049), leptin (p = 0.010) and liver PEPCK expression (p = 0.050), in which the metabolic vulnerability in the MS group was aggravated by the n-3 PUFAs deficient diet exposure. This was associated with specific alterations in the peripheral fatty acid profile. Variations in the neonatal environment interact with nutritional aspects during the life course, such as n-3 PUFAs diet content, and persistently alter the metabolic vulnerability in adulthood.

Figure 1. Mean ± SEM of the weekly chow consumption (mean consumption per cage) during the 15 weeks period of chronic exposure to the diets (from PND 35).

Maternal separated (MS) rats had increased food consumption in comparison to the non-handled (NH) ones (Repeated Measures ANOVA, p = 0.047). There was no effect of the diets on the food consumption (p = 0.245), or interaction (MS_ adequate group = 6 cages; MS_ deficient group = 6 cages; NH_ adequate group = 7 cages; NH_ deficient group = 10 cages).

Figure 2. Mean ± SEM of the weekly body weight measurements during the 15 weeks period of chronic exposure to the diets (from PND 35).

Maternal separated (MS) rats had increased body weight in comparison to the non-handled (NH) ones (Repeated Measures ANOVA, p = 0.012). There was no effect of the diets on the body weight (p = 0.099), or interaction.

Figure 3. Abdominal fat [(sum of gonadal and retroperitoneal depots' weight in grams)*100/total body weight in grams)].

Maternal separated (MS) rats had increased abdominal fat deposition in comparison to the non-handled (NH) ones (*Two-Way ANOVA, p<0.001] without effect of the diets (p = 0.756) or interaction.