Laboratory of Molecular Endocrinology, Federal University of Rio de Janeiro, CCS, Rio de Janeiro, Brazil.
Laboratory of Translational Endocrinology, Federal University of Rio de Janeiro, CCS, Rio de Janeiro, Brazil.
J Nutr Biochem. 2022 Jun;104:108976. doi: 10.1016/j.jnutbio.2022.108976. Epub 2022 Mar 1.
Maternal high-fat diet (HFD) is associated with metabolic disturbances in the offspring. Fructose is a highly consumed lipogenic sugar; however, it is unknown whether skeletal muscle of maternal HFD offspring respond differentially to a fructose overload. Female Wistar rats received standard diet (STD: 9% fat) or isocaloric high-fat diet (HFD: 29% fat) during 8 weeks before mating until weaning. After weaning, male offspring received STD and, from 120 to 150 days-old, they drank water or 15% fructose in water (STD-F and HFD-F). At 150th day, we collected the oxidative soleus and glycolytic extensor digitorum longus (EDL) muscles. Fructose-treated groups exhibited hypertriglyceridemia, regardless of maternal diet. Soleus of maternal HFD offspring showed increased triglycerides and monounsaturated fatty acid content, independent of fructose, with increased fatty acid transporters and lipogenesis markers. The EDL exhibited unaltered triglycerides content, with an apparent equilibrium between lipogenesis and lipid oxidation markers in HFD, and higher lipid uptake (fatty acid-binding protein 4) accompanied by enhanced monounsaturated fatty acid in fructose-treated groups. Mitochondrial complexes proteins and Tfam mRNA were increased in the soleus of HFD, while uncoupling protein 3 was decreased markedly in HFD-F. In EDL, maternal HFD increased ATP synthase, while fructose decreased Tfam predominantly in STD offspring. Maternal HFD and fructose induced mitochondria ultrastructural damage, intensified in HFD-F in both muscles. Thus, alterations in molecular markers of lipid metabolism and mitochondrial function in response to fructose are modified by an isocaloric and moderate maternal HFD and are fiber-type specific, representing adaptation/maladaptation mechanisms associated with higher skeletal muscle fructose-induced mitochondria injury in adult offspring.
母体高脂肪饮食（HFD）与后代的代谢紊乱有关。果糖是一种高消耗的生脂糖；然而，尚不清楚母体 HFD 后代的骨骼肌对果糖过载是否有不同的反应。雌性 Wistar 大鼠在交配前 8 周接受标准饮食（STD：9%脂肪）或等热量高脂肪饮食（HFD：29%脂肪），直至断奶。断奶后，雄性后代接受 STD，从 120 到 150 天大时，他们饮用 STD 水或 STD 水中的 15%果糖（STD-F 和 HFD-F）。在 150 天大时，我们收集了氧化比目鱼肌和糖酵解伸趾长肌（EDL）肌肉。果糖处理组表现出高甘油三酯血症，而与母体饮食无关。母体 HFD 后代的比目鱼肌显示甘油三酯和单不饱和脂肪酸含量增加，与果糖无关，脂肪酸转运蛋白和脂肪生成标志物增加。EDL 的甘油三酯含量不变，HFD 中脂肪生成和脂质氧化标志物之间似乎达到平衡，果糖处理组的脂质摄取增加（脂肪酸结合蛋白 4），并伴有单不饱和脂肪酸增加。HFD 增加了比目鱼肌的线粒体复合物蛋白和 Tfam mRNA，而 HFD-F 中解偶联蛋白 3显著减少。在 EDL 中，母体 HFD 增加了 ATP 合酶，而果糖主要在 STD 后代中降低了 Tfam。母体 HFD 和果糖诱导了两种肌肉中线粒体的超微结构损伤，在 HFD-F 中更为严重。因此，对果糖的脂质代谢和线粒体功能的分子标记的改变，是由等热量和适度的母体 HFD 引起的，并且是纤维类型特异性的，代表了与成年后代骨骼肌果糖诱导的线粒体损伤相关的适应/不适应机制。
