Early life stress interacts with the diet deficiency of omega-3 fatty acids during the life course increasing the metabolic vulnerability in adult rats.
In plain language
Early stress can change the metabolic consequences of a later diet
An early adversity may influence how the body responds to nutritional conditions encountered much later. This experiment tested whether neonatal stress and an omega-3-deficient diet combined to affect adult metabolism.
Testing two exposures at different life stages. Rat pups were either separated from their mothers for three hours a day during the first ten days of life or left undisturbed. From day thirty-five, males received a diet with adequate or deficient omega-3 fatty acids for fifteen weeks. This created four groups, allowing the researchers to distinguish effects of early separation, effects of diet and effects of their combination.
The team measured food intake, weight gain, abdominal fat and blood markers of metabolism. They also examined biological signals involved in appetite and glucose production, including a liver enzyme called PEPCK, which participates in making glucose.
The later diet had different consequences after early stress. Maternal separation was associated with greater food intake, weight gain, abdominal fat and blood triglycerides. For several other measures, the combination mattered: insulin, an index of insulin resistance, leptin and liver PEPCK expression showed interactions between early experience and dietary omega-3 availability. The deficient diet aggravated metabolic vulnerability in the previously separated animals. These changes were accompanied by differences in peripheral fatty-acid profiles.
The experiment supports a life-course account of metabolic risk. Early conditions can alter sensitivity to a subsequent diet, so a nutritional exposure may have different effects depending on developmental history. It also demonstrates why studying a single exposure at one age can miss a biologically meaningful interaction.
The comparison was between adequate and deficient diets in rats. It did not test whether adding omega-3 supplements above an adequate intake reverses early adversity, nor did it establish a treatment effect in humans. The finding concerns the interaction between developmental stress and later nutritional adequacy.
Original 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.
Reproduced from the original publication under CC BY 4.0. Wording unchanged; layout and typography normalized.
Bernardi JR, Ferreira CF, Senter G, Krolow R, de Aguiar BW, Portella AK, Kauer-Sant'anna M, Kapczinski F, Dalmaz C, Goldani MZ, Silveira PP. Early life stress interacts with the diet deficiency of omega-3 fatty acids during the life course increasing the metabolic vulnerability in adult rats. PloS one. 2013;8(4):e62031.
Read the original publication and abstract