da Silva Aragão Raquel, Guzmán-Quevedo Omar, Pérez-García Georgina, Manhães-de-Castro Raul, Bolaños-Jiménez Francisco
INRA, CHU - HôDieu, HNB1 - UMR PhAN 1280 Physiologie des Adaptations Nutritionnelles,Place Alexis Ricordeau,44096Nantes Cedex 1,France.
Departamento de Nutrição,Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Recife,Pernambuco,Brazil.
Br J Nutr. 2014 Aug 14;112(3):328-37. doi: 10.1017/S0007114514000865. Epub 2014 May 14.
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.
骨骼肌在利用燃料方面表现出显著的灵活性，以响应机体的营养摄入和能量需求。事实上，增加体力活动和禁食会触发骨骼肌细胞中的转录程序，导致从碳水化合物氧化转变为脂质氧化。据报道，代谢灵活性受损与肥胖和2型糖尿病有关，但尚不清楚无法适应代谢需求是这些病理状况的原因还是结果。鉴于生命早期不良的营养环境是成年期代谢疾病发展的一个易感因素，在本研究中，我们旨在确定母体营养不良对后代骨骼肌代谢灵活性的长期影响。为此，在整个怀孕和哺乳期喂食对照（17%蛋白质）或低蛋白（8%蛋白质，蛋白质限制（PR））饮食的母鼠所生的成年大鼠中，评估了比目鱼肌和趾长伸肌对禁食的转录反应。除了体重减轻和血浆TAG浓度降低外，PR大鼠的代谢特征与对照大鼠相同。在进食状态下，PR大鼠表现出脂肪酸氧化关键调节基因（包括CPT1a、PGC-1α、UCP3和PPARα）的表达增强，以及在禁食时增加脂肪氧化能力的基因表达受损。这些结果表明，代谢不灵活性受损先于与早期营养不良相关的代谢紊乱的发展，并可能促成其发展。
