Maternal Protein Restriction Increases Hepatic Glycogen Storage in Young Rats

Abstract

This study aimed to determine whether maternal protein restriction alters hepatic glycogen metabolism. Mated female rats were fed diets containing 20% protein throughout pregnancy and lactation (CONT), 8% protein throughout pregnancy and lactation (LP), or 8% protein during the last week of pregnancy only and lactation (LLP). Weights and lengths were reduced in the LLP and LP offspring compared with the CONT offspring. The LLP and LP offspring demonstrated reduced insulin concentrations at both 10 and 26 d and also failed to show the increase in insulin seen with time in the CONT offspring. Serum glucose and leptin levels increased with time but were not different among the groups; however, in relation to adiposity leptin levels were greater in the LLP and LP offspring at 26 d. The LLP and LP offspring had increased hepatic glycogen at day 10 (CONT, 75.1 Ϯ 9.8; LLP, 103.4 Ϯ 11.0; LP, 116.0 Ϯ 18.4 glucose residues/g tissue) and d 26 (CONT, 183.1 Ϯ 38.9; LLP, 395.3 Ϯ 16.8; LP, 396.6 Ϯ 15.1 glucose residues/g tissue). Glycogen synthase expression was increased in the LLP and LP offspring at 10 d but not 26 d; glucose transporter 2 and glycogen phosphorylase expressions were not different at either time. At 26 d glycogen synthase activity was not different; however, glycogen phosphorylase a activity was reduced. The enhanced capacity to store glycogen despite reductions in insulin secretion suggests increased insulin sensitivity possibly acting with an alternative non-insulin-dependent glycogen storage mechanism. There is now considerable evidence from animal models to support a role for maternal undernutrition in fetal programming such that alterations in metabolism during gestation or lactation result in metabolic changes in the offspring in adult life (1, 2). The thrifty phenotype hypothesis postulates that these changes occur to ensure a sufficient supply of energy to the brain and other vital organs; these changes may be beneficial in times of starvation, but detrimental in times of overnutrition in later life (3).One commonly used animal model of maternal undernutrition is the isocaloric PR rat (4). This model involves feeding dams an isocaloric diet containing only 40% of the protein of the control diet. Offspring of PR dams have been shown to develop insulin resistance as adults, with this insulin resistance being preceded by a period of improved insulin sensitivity and greater glucose tolerance (5, 6). As well as changes in whole body glucose metabolism, tissue-specific changes in gene expression and the activities of enzymes involved in glucose homeostasis have also been reported (5, 7).The timing of an insult such as PR may also be of importance. Crossover studies have suggested that the effects of protein deprivation in utero may differ from the effects of protein deprivation during lactation (7). It may also be that the final trimester of pregnancy is the crucial time of deprivation. The Dutch famine study has shown that exposure to famine throughout mid to late gestation results in reduced insulin sens...

Early undernutrition induces glucagon resistance and insulin hypersensitivity in the liver of suckling rats

“…Early undernutrition enhances insulin sensitivity in extrahepatic tissues, such as muscle and adipose tissue, in adulthood (16,18,27,45), but the impact of this restriction on the adult or immature liver has been less frequently addressed. Suckling rats from dams on hypoproteic diets throughout pregnancy and lactation show increased hepatic glycogen (21,26), as found herein in pups from globally restricted rats, indicating that this response is independent of the type of restriction. The increased amounts of GLUTs and GS and the low levels of GP suggest elevated rates of glucose uptake and glycogen production, which is supported by reduced hepatic contents of free glucose and lactate.…”

Low-protein diet disrupts the crosstalk between the PKA and PKC signaling pathways in isolated pancreatic islets

“…Although insulinemia was reduced, glycemia was unchanged in rats fed either a LP or NP diet. This finding may be due in part to a marked increase in insulin sensitivity resulting from the increased phosphorylation of the insulin receptor and insulin receptor substrate-1 as well as its association with phosphatidylinositol 3-kinase in muscle and liver tissues [3,[55][56][57][58][59]. Regarding albumin levels, humans and rats with genetic alterations that result in decreased levels of albumin show increased levels of plasma lipids and lipoproteins [60][61][62][63].…”

Early and post-weaning malnutrition impairs alpha-MSH expression in the hypothalamus: a possible link to long-term overweight

“…This same process is consistent with previous studies. [24][25][26][27] In spite that MGL-R and MPW-R rats did not show a declared obesity compared with C groups, the increased proportion of fat depots and the hyperphagia observed may have contributed to the higher ratio of body weight increase.…”