Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring
Open accessAbstract
Skeletal muscle exhibits a remarkable flexibility in the usage of fuel in response to the nutrient intake and energy demands of the organism. In fact, increased physical activity and fasting trigger a transcriptional programme in skeletal muscle cells leading to a switch from carbohydrate to lipid oxidation. Impaired metabolic flexibility has been reported to be associated with obesity and type 2 diabetes, but it is not known whether the disability to adapt to metabolic demands is a cause or a consequence of these pathological conditions. Inasmuch as a poor nutritional environment during early life is a predisposing factor for the development of metabolic diseases in adulthood, in the present study, we aimed to determine the long-term effects of maternal malnutrition on the metabolic flexibility of offspring skeletal muscle. To this end, the transcriptional responses of the soleus and extensor digitorum longus muscles to fasting were evaluated in adult rats born to dams fed a control (17 % protein) or a low-protein (8 % protein, protein restricted (PR)) diet throughout pregnancy and lactation. With the exception of reduced body weight and reduced plasma concentrations of TAG, PR rats exhibited a metabolic profile that was the same as that of the control rats. In the fed state, PR rats exhibited an enhanced expression of key regulatory genes of fatty acid oxidation including CPT1a, PGC-1α, UCP3 and PPARα and an impaired expression of genes that increase the capacity for fat oxidation in response to fasting. These results suggest that impaired metabolic inflexibility precedes and may contribute to the development of metabolic disorders associated with early malnutrition.
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Type II glycolytic muscle fiber density is higher in obese and insulin-resistant patients, although it is unknown whether this is due to inactivity or impaired glucose metabolism.
“Intriguingly, type II, glycolytic, muscle fiber density is higher in obese and insulin-resistant patients, although it is unknown whether these are due to inactivity or impaired glucose metabolism (226).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [226]
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Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
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- Authors
- da Silva Aragão, R., Guzmán-Quevedo, O., Pérez-García, G., Manhães-de-Castro, R., & Bolaños-Jiménez, F.
- Affiliations
- PhysioPathologie des Adaptations Nutritionnelles (FR)
- Venue
- British Journal Of Nutrition
- Publisher
- Cambridge University Press (CUP)
- Published
- 2014-05-14
- Volume
- 112
- Issue
- 3
- Pages
- 328-337
- ISSN
- 0007-1145 (ISSN-L)
- 1475-2662
- OpenAlex
- W2161761000
- Cited by
- 35
- References
- 44
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 1 · 2022: 7 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 2
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal Of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Me 657/09)
- Universidade Federal de Pernambuco
- Universidade de Pernambuco
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- maternal protein restriction, fatty acid oxidation, early-life malnutrition, PGC-1α, PPARα, CPT1A, UCP3, soleus muscle, extensor digitorum longus, type 2 diabetes, obesity, transcriptional regulation, offspring metabolic programming
- MeSH terms
- Uncoupling Protein 3, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Carnitine O-Palmitoyltransferase, Energy Metabolism, Enzyme Activation, Fasting, Fatty Acids, Female, Ion Channels, Lactation, Male, Oxidation-Reduction, Phenotype, Pregnancy, Prenatal Exposure Delayed Effects, Transcription Factors, Transcription, Genetic, Gene Expression, Rats, Wistar, Muscle, Skeletal, Diet, Protein-Restricted, Mitochondrial Proteins, PPAR alpha, Carbohydrate Metabolism, Lipid Metabolism, Rats, AMP-Activated Protein Kinases, Metabolome
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