Sucrose feeding during pregnancy and lactation elicits distinct metabolic response in offspring of an inbred genetic model of metabolic syndrome

Abstract

-The importance of early environment, including maternal diet during pregnancy, is suspected to play a major role in pathogenesis of metabolic syndrome and related conditions. One of the proposed mechanisms is a mismatch between the prenatal and postnatal environments, leading to misprogramming of the metabolic and signaling pathways of the developing fetus. We assessed whether the exposure to high-sucrose diet (HSD) alleviates the detrimental effects of sucrose feeding in later life (predictive adaptive hypothesis) in a highly inbred model of metabolic syndrome, the PD/Cub rat. Rat dams were continuously fed either standard or HSD (70% calories as sucrose) starting 1 wk before breeding, throughout pregnancy, at birth, and until weaning of the offspring. After weaning, all male offspring were fed HSD until the age of 20 wk, when detailed metabolic and morphometric profiles were ascertained. The early life exposure to a sucrose-rich diet resulted in distinct responses to longtime postnatal HSD feeding. Offspring of the sucrose-fed mothers displayed higher adiposity and substantial increases in triglyceride liver content together with unfavorable distribution of cholesterol into lipoprotein subfractions. On the other hand, their adiponectin concentrations were significantly higher, and insulin sensitivity of skeletal muscle was enhanced compared with the offspring of standard diet-fed mothers. Triglycerides, free fatty acids, overall glucose tolerance, and the insulin sensitivity of adipose tissue were comparable in both groups. In the genetically identical animals, maternal HSD feeding elicited a variety of subtle effects but did not lead to predictive adaptive protection from most HSD-induced metabolic derangements. developmental plasticity; animal model; PD/Cub; maternal diet GROWING EVIDENCE SUGGESTS that fetal and early life environment are determinants of disease in adult life, including dyslipidemia, insulin resistance, obesity, and hypertension (1, 26). The "thrifty phenotype" hypothesis (2) confronted the 30-yrolder "thrifty genotype" concept (28), which linked the manifestations of cardiovascular disease, insulin resistance, and diabetes in adulthood with fetal malnutrition rather than with modulation of metabolic and signaling pathways by environ-

Sucrose feeding in mouse pregnancy leads to hypertension, and sex-linked obesity and insulin resistance in female offspring

“…In contrast, the present study which investigated the effect of a maternal high sucrose diet during both prepregnancy through to suckling is arguably more relevant to the human situation. Recently, similar comparison was made in rats (Sedova et al, 2007). A high sucrose diet (70% calories as sucrose) was provided to inbred PD/Cub rats, which display a metabolic syndrome like phenotype, one week before breeding, and throughout pregnancy and suckling (Sedova et al, 2007).…”

“…Recently, similar comparison was made in rats (Sedova et al, 2007). A high sucrose diet (70% calories as sucrose) was provided to inbred PD/Cub rats, which display a metabolic syndrome like phenotype, one week before breeding, and throughout pregnancy and suckling (Sedova et al, 2007). Contrary to our observations, this study revealed no increase in maternal weight gain or food intake in SF dams compared with control dams.…”

Intrauterine nutrition: long-term consequences for vascular health

“…It was shown in humans that maternal high glycemic index of the diet during pregnancy was related to HOMA-IR, insulin, and leptin levels in the progeny at the age of 20 years 102. In an animal model, excessive maternal intake of sucrose resulted in higher adiposity, increased hepatic TG content, and elevated serum low-density lipoprotein cholesterol levels in the offspring 103. Intrauterine exposure to a fructose diet may, in turn, result in increased fasting insulin and elevated leptin and glucose levels in later life 95.…”

Prenatal high sucrose intake affected learning and memory of aged rat offspring with abnormal oxidative stress and NMDARs/Wnt signaling in the hippocampus

“…Excess energy intake during pregnancy results in programming of adverse metabolic outcomes in offspring such as obesity and diabetes in adulthood (Sedova et al, 2007). Both chronic hyperglycemia and insulin resistance may trigger neuronal death through oxidative stress and affect cognitive processes (Trevino et al, 2015).…”