Long-Lasting Effect of Perinatal Exposure to L-tryptophan on Circadian Clock of Primary Cell Lines Established from Male Offspring Born from Mothers Fed on Dietary Protein Restriction

Nascimento, Elizabeth do; Guzmán-Quevedo, Omar; Delacourt, Nellie; Aragão, Raquel da Silva; Pérez-García, Georgina; Souza, Sandra Lopes de; Manhães-de-Castro, Raul; Bolaños-Jiménez, Francisco; Kaeffer, Bertrand

doi:10.1371/journal.pone.0056231

Cited by 14 publications

(7 citation statements)

References 51 publications

(64 reference statements)

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“…One study demonstrated that MLP significantly altered the circadian expression of genes involved in the regulation of feeding and energy metabolism [21]. In addition, supplementation with the essential amino acid tryptophan has been shown to improve circadian function of cells isolated from MLP offspring [54]. Furthermore, offspring exposed to a different maternal dietary manipulation (maternal high fat diet) show changes in core circadian gene expression [55].…”

Section: Discussionmentioning

confidence: 99%

Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring

et al. 2017

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Offspring of murine dams chronically fed a protein-restricted diet have an increased risk for metabolic and neurobehavioral disorders. Previously we showed that adult offspring, developmentally exposed to a chronic maternal low-protein (MLP) diet, had lower body and hind-leg muscle weights and decreased liver enzyme serum levels. We conducted energy expenditure, neurobehavioral and circadian rhythm assays in male offspring to examine mechanisms for the body-weight phenotype and assess neurodevelopmental implications of MLP exposure. C57BL/6J dams were fed a protein restricted (8%protein, MLP) or a control protein (20% protein, C) diet from four weeks before mating until weaning of offspring. Male offspring were weaned to standard rodent diet (20% protein) and single-housed until 8–12 weeks of age. We examined body composition, food intake, energy expenditure, spontaneous rearing activity and sleep patterns and performed behavioral assays for anxiety (open field activity, elevated plus maze [EPM], light/dark exploration), depression (tail suspension and forced swim test), sociability (three-chamber), repetitive (marble burying), learning and memory (fear conditioning), and circadian behavior (wheel-running activity during light-dark and constant dark cycles). We also measured circadian gene expression in hypothalamus and liver at different Zeitgeber times (ZT). Male offspring from separate MLP exposed dams had significantly greater body fat (P = 0.03), less energy expenditure (P = 0.004), less rearing activity (P = 0.04) and a greater number of night-time rest/sleep bouts (P = 0.03) compared to control. MLP offspring displayed greater anxiety-like behavior in the EPM (P<0.01) but had no learning and memory deficit in fear-conditioning assay (P = 0.02). There was an effect of time on Per1, Per 2 and Clock circadian gene expression in the hypothalamus but not on circadian behavior. Thus, transplacental and early developmental exposure of dams to chronic MLP reduces food intake and energy expenditure, increases anxiety like behavior and disturbs sleep patterns but not circadian rhythm in adult male offspring.

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Section: Discussionmentioning

confidence: 99%

Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring

et al. 2017

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“…The rats were randomly separated into two groups (6 rats each): one group was fed a control (Ctrl) chow diet containing 18 g of protein per 100 g diet, and the second group was fed a low protein (LP) diet containing 8 g of protein plus 0.13 g of l-Trp per 100 g diet (the Ctrl diet and LP diet contained the same amount of l-Trp) (Nascimento et al 2013). Dams were maintained under controlled conditions (22 °C, 12 h/12 h dark/light cycle) with free access to their experimental diets and tap water until the evening of the 12th (embryonic day 12: E12) or until the 19th day of gestation (E19).…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Maternal and fetal tryptophan metabolism in gestating rats: effects of intrauterine growth restriction

et al. 2015

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L-Tryptophan (L-Trp) is a precursor for serotonin (5-HT) and nicotinamide adenine dinucleotide (NAD) synthesis. Both 5-HT and NAD may impact energy metabolism during gestation given that recent studies have demonstrated that increased 5-HT production is crucial for increasing maternal insulin secretion, and that sirtuin, an NAD(+)-dependent protein deacetylase, regulates endocrine signaling. Infants born with intrauterine growth restriction (IUGR) are at a higher risk of metabolic disease once they reach adulthood. IUGR is associated with altered maternal-fetal amino acid transfer. Whether IUGR affects L-Trp metabolism in mother and fetus has not been fully elucidated. Recently, we developed an analytical method using stable isotope-labeled L-Trp to explore the metabolism of L-Trp and its main metabolites, L-kynurenine (L-Kyn), 5-HT and quinolinic acid (QA). In this study, dams submitted to dietary protein restriction throughout gestation received intravenous infusions of stable isotope-labeled (15)N2-L-Trp to determine whether L-Trp metabolism is affected by IUGR. Samples were obtained from maternal, fetal and umbilical vein plasma, as well as the amniotic fluid (AF), placenta and liver of the mother and the fetus after isotope infusion. We observed evidence for active L-Trp transfer from mother to fetus, as well as de novo synthesis of 5-HT in the fetus. Plasma 5-HT was decreased in undernourished mothers. In IUGR fetuses, maternal-fetal L-Trp transfer remained unaffected, but conversion to QA was impaired, implying that NAD production also decreased. Whether such alterations in tryptophan metabolism during gestation have adverse consequences and contribute to the increased risk of metabolic disease in IUGR remains to be explored.

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“…14,30 These changes in both litter size and/or birth weight depend on food quality and macronutrient content, as well as the energy value of the maternal diet. [31][32][33] Recently, we reported that administering a low-protein diet through pregnancy and lactation does not alter pup birth weight, but does reduce the food intake of dams during lactation. 33 However, we did not observe any differences in food intake between lactating rats that received either the C or LE diet.…”

Section: Discussionmentioning

confidence: 99%

“…[31][32][33] Recently, we reported that administering a low-protein diet through pregnancy and lactation does not alter pup birth weight, but does reduce the food intake of dams during lactation. 33 However, we did not observe any differences in food intake between lactating rats that received either the C or LE diet. Similar levels of intake were noted between our groups of lactating rats.…”

Section: Discussionmentioning

confidence: 99%

Unlimited access to low-energy diet causes acute malnutrition in dams and alters biometric and biochemical parameters in offspring

Nascimento

Muniz

et al. 2013

J Dev Orig Health Dis

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Here we analyze the outcomes of unlimited access to a low-energy (LE) diet in dams and their offspring. At 3 weeks' gestation, pregnant Wistar rats were divided into two groups: (1) the control group received a normoenergetic diet; and (2) the experimental group received the LE diet. In dams, lactation outcomes, food intake, body weight, plasma IGF-1, prealbumin, transferrin and retinol-binding protein levels were evaluated; in offspring, biometric and biochemical parameters and food intake were evaluated. No differences were observed during pregnancy. However, after lactation, dams that received the LE diet demonstrated significant reductions in body weight (P<0.05), plasma IGF-1 (P=0.01), prealbumin and visceral fat (P<0.001). Pups born to dams that received the LE diet demonstrated reduced body length and weight at weaning (P<0.001) and were lighter than the control animals at the end of the experimental period. Pups also demonstrated reduced plasma, low-density lipoprotein (P=0.04), triglycerides (P=0.002) and glucose levels (P<0.05), and differences were noted in visceral fat. These results indicate that feeding dams with LE diet during the reproductive period induces acute malnutrition and impairs the growth and development of offspring, as well as certain metabolic parameters.

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Long-Lasting Effect of Perinatal Exposure to L-tryptophan on Circadian Clock of Primary Cell Lines Established from Male Offspring Born from Mothers Fed on Dietary Protein Restriction

Cited by 14 publications

References 51 publications

Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring

Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring

Maternal and fetal tryptophan metabolism in gestating rats: effects of intrauterine growth restriction

Unlimited access to low-energy diet causes acute malnutrition in dams and alters biometric and biochemical parameters in offspring

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