Long-term effects on pancreatic function of feeding a HC formula to rats during the preweaning period

Vadlamudi, Satyaprasad; Hiremagalur, Bhargava; Tao, Ling; Kalhan, Satish C.; Kalaria, Rajesh N.; Kaung, Hue Lee C; Patel, Mulchand S.

doi:10.1152/ajpendo.1993.265.4.e565

Cited by 34 publications

(59 citation statements)

References 19 publications

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“…However, the low blood glucose and high GK activity observed in our animals do not support a state of insulin dysregulation. In suckling rats, a high carbohydrate diet was shown to induce, later in life, chronic hyperinsulinemia (39) and poor tolerance to oral glucose challenge (39,40). A chronically high secretion of insulin could explain our observation of low blood glucose and high GK activity.…”

Section: Discussionmentioning

confidence: 68%

Neonatal Exposure to Oxidants Induces Later in Life a Metabolic Response Associated to a Phenotype of Energy Deficiency in an Animal Model of Total Parenteral Nutrition

et al. 2010

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Failure to protect total parenteral nutrition (TPN) from ambient light exacerbates the generation of peroxides, which affects blood glucose and plasma triacylglyceride (TG) in neonates. Based on the concept that the origin of adult diseases can be traced back to perinatal life, it was hypothesized that neonatal exposure to peroxides may affect energy availability later in life. Three-day-old guinea pigs, fitted with a jugular catheter, were fed regular chow (sham) Ϯ i. T he association between oxidative stress and characteristic features of the metabolic syndrome, such as diabetes, hypertension, and dyslipidemia, is well documented (1-6). Human (7) and animal studies (8,9) suggest that the origin of the metabolic syndrome can be traced back to perinatal life, a time when newborn infants are at greater risk of oxidative stress caused by weak antioxidant defenses (10 -12) or exposure to an oxidative environment or both (13-18). Several reports suggest that, in neonates, oxidative stress triggers the events that lead to programming of adult diseases (19 -22).Total parenteral nutrition (TPN) represents a source of oxidants in the form of peroxides that can be calibrated either by applying or not photoprotecting. The peroxides are derived from interactions between dissolved oxygen and electron donors such as lipid, amino acid, or ascorbic acid (23,24). The reaction is catalyzed by photoexcited riboflavin (24). Therefore, the main active agents participating in the generation of peroxides in TPN are ambient light [(ϩ)L] and multivitamin preparations (MVP) (23,24). Photoprotection [(Ϫ)L] of TPN reduces the levels of peroxides by close to 50% (23,25,26). Absence of photoprotection of TPN is associated in preterm newborn infants with higher urinary peroxide concentrations (16), higher blood pressure in girl babies (15), and greater blood glucose and plasma triacylglycerol concentrations (13). Hence, peroxides contaminating TPN solutions are not completely quenched by newborns infants and are thought to be an agent initiating metabolic perturbations. We questioned whether these peroxides are linked to metabolic consequences later in life.Based on the concept that neonatal oxidative stress may interfere with metabolic programming (27), we hypothesized that neonatal exposure to peroxides such as those generated in solutions of parenteral nutrition, induces a permanent modification in lipid and glucose metabolism especially lipogenesis and/or glycolysis. Perturbations in lipid and glucose metabolism, which are fuels for energy production, could have longterm consequences on growth and physical activity, thereby affecting global development. The aim of this study was to measure in adult guinea pigs metabolic responses and spontaneous physical activity after a brief neonatal exposure to i.v. oxidant molecules limited to the first wk of life. A second objective was to assess if these modifications were related to the infusion of peroxides. MATERIALS AND METHODSExperimental design. The metabolic response and the levels...

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Section: Discussionmentioning

confidence: 68%

Neonatal Exposure to Oxidants Induces Later in Life a Metabolic Response Associated to a Phenotype of Energy Deficiency in an Animal Model of Total Parenteral Nutrition

et al. 2010

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“…The molecular changes (increase in the preproinsulin gene transcription) observed in islets from neonatal HC rats are also observed in adult HC islets (32). There is an increase in the insulin-producing mass of the adult HC pancreas (17). Chronic hyperinsulinemia is accompanied by an increase in the body weight of the animals from day 55 onward and full blown obesity by day 100 (15) (Fig.…”

Section: Programming Of Early Onset Adaptations Into Adulthoodmentioning

confidence: 82%

Metabolic Programming: Causes and Consequences

Patel

Srinivasan

2002

Journal of Biological Chemistry

114

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The normal programmed development of a multicellular organism from the germ cell is a synchronized series of events driven by genetic instructions acquired during conception. During the early critical periods in life the organism also has the ability to respond to environmental situations that are alien to normal development by adaptations at the cellular, molecular, and biochemical levels. Such early adaptations to a nutritional stress/stimulus permanently change the physiology and metabolism of the organism and continue to be expressed even in the absence of the stimulus/stress that initiated them, a process termed "metabolic programming" (1). A brief summary of the findings from human epidemiological and animal studies is presented below in support of the concept of metabolic programming induced by nutritional experiences during critical periods in development with consequences later in adulthood. For detailed accounts the reader is referred to excellent reviews on this subject (2-5). This minireview will focus on metabolic programming with reference to a novel rat model developed in our laboratory. Evidence for Metabolic Programming from Human Epidemiological DataExtensive epidemiological findings indicate that metabolic programming occurs in humans. Barker (6) was the first to suggest from epidemiological studies that the disproportionate size of the newborn resulting from maternal malnutrition correlated with an increased risk for adverse health outcomes (type II diabetes, hypertension, and cardiovascular diseases) later in adult life. These primary observations resulted in the now widely recognized "fetal origins" hypothesis emphasizing the importance of adequate maternal nutrition during pregnancy (4). Evidence for Metabolic Programming in AnimalsNutritional programming has been demonstrated in animal studies. In pioneering studies with rodents, McCance (7) demonstrated by adjusting litter size that the quantity of food consumed during early periods of postnatal life has long term consequences on growth. The consequences of maternal malnutrition induced by either a low protein diet or caloric restriction during gestation and lactation cause major changes in the structure and function of several organs in the offspring. Pregnant rats fed a low protein diet produced pups with alterations in pancreatic islets (8, 9). These include reduced islet vascularization, ␤ cell proliferative capacity, and islet size with rightward shift (decreased sensitivity) in glucose-stimulated insulin secretion and altered sensitivity to insulin in muscle (8, 9). Furthermore, hypothalamic nuclei are malformed in these weanling rats; this is accompanied by reduced vascularization of the cerebral cortex in the progeny (10). Metabolic capacities of the liver, muscle, and adipose tissue are compromised by maternal protein restriction during gestation and lactation with adverse adult onset outcomes (11). Elevated insulin concentrations during critical periods of development, as occurs perinatally in the offspring of gestationally dia...

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“…We have developed a rat model for adult-onset obesity by rearing 4-day-old rat pups on a HC milk formula (56% of the calories from carbohydrate compared with 8% in rat milk) up to postnatal day 24 when they are weaned on a standard rodent diet (19,26). The mere switch in the major source of calories from fat in rat milk to carbohydrate in the HC milk formula without alterations in total caloric intake results in the immediate onset of hyperinsulinemia, its persistence even after its withdrawal on postnatal day 24, and adult-onset obesity occurring in both male and female rats (9,10,28). A significant observation from these studies was that firstgeneration female rats (1-HC) that were artificially reared on the HC milk formula in their immediate postnatal period spontaneously transmitted the HC phenotype of chronic hyperinsulinemia and adult-onset obesity to their progeny (2nd generation HC; 2-HC) without the necessity for any dietary intervention in 2-HC rats (29).…”

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confidence: 99%

Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype

Srinivasan¹,

Aalinkeel²,

Song³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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. Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype. Am J Physiol Endocrinol Metab 290: E129 -E134, 2006. First published September 6, 2005 doi:10.1152/ajpendo.00248.2005We have previously shown that artificial rearing of newborn female rat pups on a high-carbohydrate (HC) milk formula resulted in chronic hyperinsulinemia and adultonset obesity (HC phenotype) and that the maternal HC phenotype was transmitted to their progeny (2-HC rats) because of fetal development in the HC female rat. The aims of this study were to investigate 1) the fetal adaptations that predisposed the progeny for the expression of the HC phenotype in adulthood and 2) whether the transfer of the HC phenotype to the progeny could be reversed by maternal food restriction. Fetal parameters such as plasma insulin and glucose levels, mRNA level of preproinsulin gene, pancreatic insulin content, and islet insulin secretory response in vitro were determined. On gestational day 21, 2-HC fetuses were hyperinsulinemic, had increased insulin content and mRNA level of the preproinsulin gene in their pancreata and demonstrated an altered glucose-stimulated insulin secretory response by isolated islets. Modification of the intrauterine environment in HC female rats was achieved by pair feeding them to the amount of diet consumed by age-matched control rats from the time of their weaning. This mild dietary restriction reversed their HC phenotype and also prevented the development of the HC phenotype in their progeny. These findings show that malprogramming of the progeny of the hyperinsulinemic-obese HC female for the expression of the HC phenotype is initiated in utero and that normalization of the maternal environment in HC female rats by mild food restriction resulted in the normal phenotype in their progeny. maternal intrauterine environment; fetal programming; fetal hyperinsulinemia; obesity; pair feeding EPIDEMIOLOGICAL DATA AND RESULTS from animal models indicate that the nutritional status of the mother during pregnancy impacts on the expression of metabolic diseases in adulthood of the progeny (2,3,7,11,12,18,21,30). Extensive organ development continues to occur in the immediate postnatal life of the rat, suggesting that this period, too, is vulnerable for metabolic programming effects. Earlier, we showed that the overlap of an altered nutritional experience in the form of a high-carbohydrate (HC) milk formula with the critical window of postnatal organ development in neonatal rat pups resulted in the establishment of the HC phenotype (chronic hyperinsulinemia and adult-onset obesity) in these rats (19,26). Because of fetal development in HC female rats, adult progeny demonstrated the same HC phenotype (29). Whether the adaptations that predispose the progeny for expression of the HC phenotype in adult life occur during fetal development in the HC intrauterine environment was not explored in the earlier study.The suckling period in the rat ...

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Long-term effects on pancreatic function of feeding a HC formula to rats during the preweaning period

Cited by 34 publications

References 19 publications

Neonatal Exposure to Oxidants Induces Later in Life a Metabolic Response Associated to a Phenotype of Energy Deficiency in an Animal Model of Total Parenteral Nutrition

Neonatal Exposure to Oxidants Induces Later in Life a Metabolic Response Associated to a Phenotype of Energy Deficiency in an Animal Model of Total Parenteral Nutrition

Metabolic Programming: Causes and Consequences

Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype

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