Research Support Unit, Hospital General La Mancha Centro, 13600 Alcázar de San Juan, Spain.
Instituto de Investigación de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain.
Int J Mol Sci. 2023 Sep 22;24(19):14443. doi: 10.3390/ijms241914443.
Early overnutrition is associated with cardiometabolic alterations in adulthood, likely attributed to reduced insulin sensitivity due to its crucial role in the cardiovascular system. This study aimed to assess the long-term effects of early overnutrition on the development of cardiovascular insulin resistance. An experimental childhood obesity model was established using male Sprague Dawley rats. Rats were organized into litters of 12 pups/mother (L12-Controls) or 3 pups/mother (L3-Overfed) at birth. After weaning, animals from L12 and L3 were housed three per cage and provided access to food for 6 months. L3 rats exhibited elevated body weight, along with increased visceral, subcutaneous, and perivascular fat accumulation. However, heart weight at sacrifice was reduced in L3 rats. Furthermore, L3 rats displayed elevated serum levels of glucose, leptin, adiponectin, total lipids, and triglycerides compared to control rats. In the myocardium, overfed rats showed decreased IL-10 mRNA levels and alterations in contractility and heart rate in response to insulin. Similarly, aortic tissue exhibited modified gene expression of TNFα, iNOS, and IL-6. Additionally, L3 aortas exhibited endothelial dysfunction in response to acetylcholine, although insulin-induced relaxation remained unchanged compared to controls. At the molecular level, L3 rats displayed reduced Akt phosphorylation in response to insulin, both in myocardial and aortic tissues, whereas MAPK phosphorylation was elevated solely in the myocardium. Overfeeding during lactation in rats induces endothelial dysfunction and cardiac insulin resistance in adulthood, potentially contributing to the cardiovascular alterations observed in this experimental model.
早期营养过剩与成年人心血管代谢改变有关，这可能归因于胰岛素敏感性降低，因为胰岛素在心血管系统中起着至关重要的作用。本研究旨在评估早期营养过剩对心血管胰岛素抵抗发展的长期影响。采用雄性 Sprague Dawley 大鼠建立了一种实验性儿童肥胖模型。出生时，将大鼠分为每窝 12 只幼鼠/母鼠（L12-对照组）或 3 只幼鼠/母鼠（L3-过度喂养组）。断奶后，L12 和 L3 的动物每笼三只饲养，并提供 6 个月的食物。L3 大鼠体重增加，内脏、皮下和血管周围脂肪堆积增加。然而，L3 大鼠的心脏重量在处死时降低。此外，与对照组相比，L3 大鼠的血清葡萄糖、瘦素、脂联素、总脂质和甘油三酯水平升高。在心肌中，过度喂养的大鼠显示 IL-10 mRNA 水平降低，以及对胰岛素的收缩性和心率反应改变。同样，主动脉组织显示 TNFα、iNOS 和 IL-6 的基因表达改变。此外，L3 主动脉对乙酰胆碱表现出内皮功能障碍，尽管与对照组相比，胰岛素诱导的舒张保持不变。在分子水平上，L3 大鼠对胰岛素的 Akt 磷酸化反应降低，无论是在心肌还是主动脉组织中，而 MAPK 磷酸化仅在心肌中升高。哺乳期大鼠过度喂养会导致成年后内皮功能障碍和心脏胰岛素抵抗，这可能是该实验模型中观察到的心血管改变的原因。
