Abstract | BACKGROUND AIMS: Maternal undernutrition programs metabolic adaptations which are ultimately detrimental to adult. L-tryptophan supplementation was given to manipulate the long-term sequelae of early-life programming by undernutrition and explore whether cultured cells retain circadian clock dysregulation. METHODS: Male rat pups from mothers fed on low protein (8%, LP) or control (18%, CP) diet were given, one hour before light off, an oral bolus of L-tryptophan (125 mg/kg) between Day-12 and Day-21 of age. Body weight, food intake, blood glucose along with the capacity of colonization of primary cells from biopsies were measured during the young (45-55 days) and adult (110-130 days) phases. Circadian clock oscillations were re-induced by a serum shock over 30 hours on near-confluent cell monolayers to follow PERIOD1 and CLOCK proteins by Fluorescent Linked ImmunoSorbent Assay (FLISA) and period1 and bmal1 mRNA by RT-PCR. Cell survival in amino acid-free conditions were used to measure circadian expression of MAP-LC3B, MAP-LC3B-FP and Survivin. RESULTS:
Tryptophan supplementation did not alter body weight gain nor feeding pattern. By three-way ANOVA of blood glucose, sampling time was found significant during all phases. A significant interaction between daily bolus ( Tryptophan, saline) and diets (LP, CP) were found during young (p = 0.0291) and adult (p = 0.0285) phases. In adult phase, the capacity of colonization at seeding of primary cells was twice lower for LP rats. By three-way ANOVA of PERIOD1 perinuclear/nuclear immunoreactivity during young phase, we found a significant effect of diets (p = 0.049), daily bolus (p<0.0001) and synchronizer hours (p = 0.0002). All factors were significantly interacting (p = 0.0148). MAP-LC3B, MAP-LC3B-FP and Survivin were altered according to diets in young phase. CONCLUSIONS: Sequelae of early-life undernutrition and the effects of L-tryptophan supplementation can be monitored non-invasively by circadian sampling of blood D-glucose and on the expression of PERIOD1 protein in established primary cell lines.
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Authors | Elizabeth Nascimento, Omar Guzman-Quevedo, Nellie Delacourt, Raquel da Silva Aragão, Georgina Perez-Garcia, Sandra Lopes de Souza, Raul Manhães-de-Castro, Francisco Bolaños-Jiménez, Bertrand Kaeffer |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 2
Pg. e56231
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23460795
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- Blood Glucose
- Tryptophan
- Tryptophan Hydroxylase
- CLOCK Proteins
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Topics |
- Aging
(blood, metabolism)
- Animals
- Animals, Newborn
- Autophagy
(drug effects)
- Biomarkers
(metabolism)
- Blood Glucose
(drug effects, metabolism)
- CLOCK Proteins
(genetics, metabolism)
- Cell Adhesion
(drug effects)
- Cell Line
- Circadian Clocks
(drug effects)
- Colony-Forming Units Assay
- Diet, Protein-Restricted
- Energy Metabolism
(drug effects)
- Feeding Behavior
(drug effects)
- Female
- Intra-Abdominal Fat
(anatomy & histology, drug effects)
- Lactation
(drug effects)
- Male
- Maternal Exposure
- Phenotype
- Pregnancy
- Rats
- Serum
(metabolism)
- Tryptophan
(pharmacology)
- Tryptophan Hydroxylase
(metabolism)
- Weight Gain
(drug effects)
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