Effect of maternal low-protein diet and taurine on the vulnerability of adult Wistar rat islets to cytokines

Abstract

Aims/hypothesis. A maternal low-protein diet has been shown to induce an increased susceptibility of fetal islets to cytokines, but this effect can be avoided by maternal taurine supplementation. Here, we question whether these effects persist until adulthood in the offspring, despite the animal having a normal diet after weaning. Methods. Pregnant Wistar rats received a diet of either 20% or 8% protein (control [C group] and recuperated [R group] respectively), which was or was not supplemented with taurine (control treated with taurine [CT group] and recuperated treated with taurine [RT group] respectively) during gestation and lactation. When the female offspring reached adulthood, an OGTT was performed. In a second stage, islets were isolated from these offspring, then pretreated or not with taurine, and subsequently treated with cytokines. Results. Fasting glycaemia was higher (p<0.05) and insulinaemia was lower (p<0.01) in the R group than in the C group. Taurine supplementation decreased insulinaemia in the CT group and tended to increase it in the RT group. After the OGTT, glycaemia in R animals was not different from that in the C group, despite a blunted insulin response (p<0.05) which was restored by taurine. Supplementation in C-group mothers led to a weak glucose intolerance. In vitro, more apoptotic cells were observed in R islets after cytokines treatment (p<0.01). The addition of taurine to the culture medium in the R and C groups protected the islets from the cytokines (p<0.01). Maternal taurine supplementation decreased the sensitivity of islets in the RT group (p<0.01), but increased sensitivity in the CT group (p<0.01). Conclusions/interpretation. The increased vulnerability of islets to cytokines due to a restriction of protein during fetal development was still evident when the offspring reached adulthood. The low-protein diet also induced hyperglycaemia in the presence of lower insulinaemia. Taurine supplementation protected adult islets of the R group from cytokine toxicity and restored the insulinaemia. However, unnecessary supplementation of taurine could have detrimental effects.

Effects of Taurine Supplementation on Hepatic Markers of Inflammation and Lipid Metabolism in Mothers and Offspring in the Setting of Maternal Obesity

“…Our findings suggest that maternal taurine supplementation may protect the offspring of obese mothers against developmentally programmed NAFLD despite worsening maternal postpartum fatty liver disease. While a few other studies investigated reversing the programming effects in offspring of undernutrition models [20]–[22], [68]–[70], our study first reports the reversing effect in a model of maternal obesity. Together, these studies indicate that the early period of life may be a critical window for reversing programming effects.…”

“…We did not observe any significant changes in neonatal glucose concentrations in the present study but there was a significant reduction in birthweight in female but not male offspring of taurine supplemented dams. Taurine supplementation in vivo has been reported to protect islets in offspring from low protein fed dams from cytokine toxicity, but increase islet sensitivity to cytokines and impair pancreatic development in control animals [21], [22]. Therefore, possible taurine toxicity in the setting of normal pregnancy outcomes should be further investigated.…”

“…Pregnant rats were then housed individually with free access to food and water and maintained at 25°C and a 12 h light: 12 h darkness cycle. Animals were randomly assigned to one of four nutritional groups: control group (CON) fed a standard chow diet (Diet 2018, 24% calories from protein, 18% from fat, 58% from carbohydrate, Harlan Teklad, Blackthorn, Bicester, UK) ad-libitum throughout pregnancy and lactation (n = 9); control taurine group (CT) fed standard chow diet with additional 1.5% w/v taurine supplementation in drinking water [20], [22] (n = 7); maternal obesogenic diet group (MO) fed a high-fat high-fructose diet (20% calories from protein, 45% from fat, 35% from carbohydrate (including 26% from fructose); Diet D03101602, Research Diets, NJ, USA; n = 8); maternal obesogenic diet and taurine group (MOT) fed the obesogenic diet with additional 1.5% w/v taurine supplementation in drinking water (n = 8).…”

“…Reports suggest that taurine supplementation can enhance insulin sensitivity through modification of insulin signaling enzymes in fructose-fed rats [19]. Furthermore, maternal taurine supplementation to low protein mothers has been documented to normalise pancreatic islet development in offspring with normalisation of glucose and insulin homeostasis in later life [20]–[22]. These beneficial effects on glucose metabolism have been shown to persist into adult life [23].…”

Impaired Hypothalamic mTOR Activation in the Adult Rat Offspring Born to Mothers Fed a Low-Protein Diet

“…Several tissue and cellular dysfunctions have been proposed as underlying mechanisms of the developmental programming of the metabolic syndrome including altered organ structure [12], [13], elevated glucocorticoids and endocrine sensitivity [14], [15], impaired mitochondrial function [16], [17], altered feeding behaviour [18], [19] and impaired gene expression resulting from the detrimental effects of perinatal malnutrition on the epigenome [20]–[22]. Strikingly, maternal nutrient restriction, maternal obesity, neonatal overfeeding or neonatal malnutrition, all result in common physio-pathological outcomes in adulthood [21], [23], [24].…”