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Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring

Abstract : 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-1 alpha, UCP3 and PPAR alpha 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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Submitted on : Wednesday, May 27, 2020 - 11:01:39 PM
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Raquel da Silva Aragao, Omar Guzman Quevedo, Georgina Perez-Garcia, Raul Manhães-De-Castro, Francisco Bolaños-Jiménez. Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring. British Journal of Nutrition, Cambridge University Press (CUP), 2014, 112 (3), pp.328-337. ⟨10.1017/S0007114514000865⟩. ⟨hal-02637429⟩



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