Protein Restriction During the Last Third of Pregnancy Malprograms the Neuroendocrine Axes to Induce Metabolic Syndrome in Adult Male Rat Offspring

Abstract

Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P < .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P < .05) with higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P < .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol.

Monosodium l‐glutamate‐obesity onset is associated with disruption of central control of the hypothalamic‐pituitary‐adrenal axis and autonomic nervous system

“…One day after i.c.v. treatment, a subset of rats from each group (n = 15‐25 rats for each group) underwent a surgical procedure for the ivGTT, as described previously . After 12 hour of fasting, a glucose load (1 g kg ‐1 BW) was infused cia the cannula into the bloodstream of the rats.…”

“…The plasma glucose concentration was measured following the glucose oxidase method using a commercial kit (Gold Analisa Diagnóstica, Belo Horizonte, MG, Brazil). The insulin concentration was quantified using a radioimmunoassay kit and a gamma counter (Wizard 2 Automatic Gamma Counter, 2470 Model; PerkinElmer, Shelton, CT, USA) with 125 I‐labelled recombinant human insulin (PerkinElmer ® , Shelton, CT, USA), as described previously ; leptinaemia and corticosteronaemia levels were measured using commercial enzyme‐linked immunosorbent assay (ELISA) kits (Enzo Life Sciences, Plymouth Meeting, PA, USA). The intra‐ and interassay coefficients of variation were 9.8% and 12.2% for insulin, 5.9% and 7.2% for leptin, and 7.7% and 9.7% for corticosterone.…”

Fish oil supplementation during adolescence attenuates metabolic programming of perinatal maternal high-fat diet in adult offspring

“…Both diets contained approximately 16⋅3 kJ/g of energy (isoenergetic) and their macronutrients compositions are described at Table 2. The HFD was composed by a moderate increased lipid content with protein and carbohydrate contents within the range recommended for rodents (AIN-93), which avoided the negative impact of lowprotein or low-carbohydrate diets (35,36) . The differences between macronutrient compositions of diets were not tested statistically, because we estimated the diet composition by ingredients composition described at ingredient label.…”

The role of adipokines in developmental programming: evidence from animal models

“…Studies in rodents have provided evidence for adiponectin acting as a link between maternal adipose tissue and fetal growth via regulation of placental function (Aye et al 2013). In adult male rat offspring of LP-fed mothers, adiponectin concentrations are reduced concomitant with insulin resistance, hyperphagia and increased visceral adiposity (Silvestre et al 2014, De Oliveira et al 2016. In the LP model used by Silvestre et al, adiponectin and adiponectin receptor expression was reduced in offspring adipose tissue, along with levels of peroxisome proliferatoractivated receptor (PPAR)-α and activity of AMP-activated protein kinase (AMPK) which are downstream targets of adiponectin.…”