Post-weaning protein malnutrition in the rat produces short and long term metabolic impairment, in contrast to earlier and later periods

Abstract

Malnutrition during gestation and lactation modifies metabolic strategies and leads to metabolic disease in adult life. Studies in human populations suggest that malnutrition during infancy may also induce long term metabolic disorders.The present study investigated if post-weaning and a late period of development might be sensitive for long term metabolic impairment. Hereto male Wistar rats were malnourished with a low protein diet (6%), during gestation and lactation (MGL), from weaning to 55 days (MPW) or during adulthood from 90 to 120 days (MA). Control rats (C) were fed with a regular diet (23% protein). We determine plasma concentrations of insulin, glucagon, triacylglycerols (TAG), free fatty acids (FFA), and liver glycogen after a Glucose Tolerance Test (GTT).Independent of the age of onset, malnutrition induced low body weight. Early and post-weaning malnutrition produced impaired glucose tolerance and low values of TAG, also in MPW induced low values of insulin and glucagon. At 90 days, after balanced diet rehabilitation, the MGL group showed a similar glucose tolerance test as the controls but display low values of insulin, while the MPW group exhibited high levels of glucose and TAG, and low values of insulin, glucagon, FFA and hepatic glycogen. At 180 days, after balanced rehabilitation only MPW rats showed metabolic alterations. Malnutrition during adult life (MA) did not produce metabolic disturbances. Surprisingly the results uncover the post-weaning stage as a vulnerable period to malnutrition that induces long lasting metabolic alterations and deficiency in pancreatic function.

Keywords: critical period; development; insulin; metabolic disease; nutritional rehabilitation; pancreas..

Figure 1

Schematic representation of the experimental groups. Arrows represent the life span of rats with G = gestation and L = lactation. Day of birth is indicated by the short dotted line. Striped areas represent the intervals in which rats of different groups were exposed to the 6% protein diet, while white areas represent exposure to the 23% protein balanced diet. Vertical lines represent selected ages for GTT and blood sampling.

Figure 2

Body weight of A) rats malnourished during gestation and lactation and rehabilitated from weaning to 180 days (MGL group; n = 7) B) rats malnourished from weaning to 55 days and rehabilitated until 180 days (MPW group; n = 7) and C) rats malnourished from 90 to 120 days and rehabilitated (MA group; n = 7). Control rats are represented with the black continuous line, while malnourished groups are represented with dotted line. The striped box represents the malnutrition interval. Values are given as means ± SEM. * show statistical difference (p ≤ 0.05), only males were used for the experiment.

Figure 3

The absolute glucose increase (mean ± SEM) during Glucose Tolerance Test. Left column represents groups after an acute stage of malnutrition; A) MGL at 25 days; D) MPW at 55 days and G) MA at 120 days. The middle column represents the GTT values after short term rehabilitation: B) MGL and E) MPW rats evaluated at 90 days and H) MA rats evaluated at 180 days. The right column represents the glucose values after long term rehabilitation C) MGL and F) MPW at 180 days of age. * indicates statistical difference (p ≤ 0.003); n = 7 for all groups.

Figure 4

Plasma insulin concentration after GTT. Values are presented as mean ± SEM; n = 5-7. Left panel of graphics represent the values at the end of malnutrition stage for A) MGL, D) MPW and G) MA groups. Central panels showed the hormone concentration after short term rehabilitation; B) MGL, E) MPW and H) MA groups; the right graphics represents the insulin values after long term balance rehabilitation for C) MGL and F) MPW groups. Statistical difference between the control (black bars) and the malnourished groups (white bars) is indicated * p ≤ 0.05.

Figure 5

Mean ± SEM of plasma glucagon concentration after GTT. Asterisk indicates statistical difference between C and MPW groups (p ≤ 0.03; n = 5-7). For other indications see Fig. 3 and 4.

Figure 6

Plasma concentration of triacylglycerols (TAG) after GTT. Values are presented as mean ± SEM, n = 7. Statistical difference between the control (black bars) and the malnourished groups (white bars) is indicated * p ≤ 0.05. For details see fig. 3 and 4.

Figure 7

Plasma concentration of free fatty acids (FFA) in control and malnourished rats at the end of GTT are presented as mean ± SEM (n = 7). Indications as in figure 3 and 4. Statistical difference is indicated by * p ≤ 0.03.

Figure 8

Hepatic glycogen concentration per gram of tissue (mean ± SEM; n = 7) after GTT. Indications as in Fig. 3 and 4. * denoted statistical significance p = 0.05.