Velasco Myrian, Ortiz-Huidobro Rosa Isela, Larqué Carlos, Sánchez-Zamora Yuriko Itzel, Romo-Yáñez José, Hiriart Marcia
Neuroscience Division, Department of Cognitive Neuroscience, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Department of Embryology and Genetics, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Endocr Connect. 2020 Sep;9(9):890-902. doi: 10.1530/EC-20-0288.
We assessed the sex-specific differences in the molecular mechanisms of insulin resistance in muscle and adipose tissue, in a MS rat model induced by a high sucrose diet.
Male, female, and ovariectomized female Wistar rats were randomly distributed in control and high-sucrose diet (HSD) groups, supplemented for 24 weeks with 20% sucrose in the drinking water. At the end, we assessed parameters related to MS, analyzing the effects of the HSD on critical nodes of the insulin signaling pathway in muscle and adipose tissue.
At the end of the treatment, HSD groups of both sexes developed obesity, with a 15, 33 and 23% of body weight gain in male, female, and OVX groups respectively, compared with controls; mainly related to hypertrophy of peripancreatic and gonadal adipose tissue. They also developed hypertriglyceridemia, and liver steatosis, with the last being worse in the HSD females. Compared to the control groups, HSD rats had higher IL1B and TNFA levels and insulin resistance. HSD females were more intolerant to glucose than HSD males. Our observations suggest that insulin resistance mechanisms include an increase in phosphorylated AKT(S473) form in HSD male and female groups and a decrease in phosphorylated P70S6K1(T389) in the HSD male groups from peripancreatic adipose tissue. While in gonadal adipose tissue the phosphorylated form of AKT decreased in HSD females, but not in HSD males. Finally, HSD groups showed a reduction in p-AKT levels in gastrocnemius muscle.
A high-sucrose diet induces MS and insulin resistance with sex-associated differences and in a tissue-specific manner.
我们在高蔗糖饮食诱导的代谢综合征（MS）大鼠模型中，评估了肌肉和脂肪组织中胰岛素抵抗分子机制的性别差异。
将雄性、雌性及去卵巢雌性Wistar大鼠随机分为对照组和高蔗糖饮食（HSD）组，饮用水中添加20%蔗糖，持续24周。最后，我们评估了与MS相关的参数，分析了HSD对肌肉和脂肪组织中胰岛素信号通路关键节点的影响。
治疗结束时，两性的HSD组均出现肥胖，与对照组相比，雄性、雌性和去卵巢组体重分别增加了15%、33%和23%；主要与胰腺周围和性腺脂肪组织肥大有关。它们还出现了高甘油三酯血症和肝脂肪变性，后者在HSD雌性大鼠中更严重。与对照组相比，HSD大鼠的IL1B和TNFA水平更高，且存在胰岛素抵抗。HSD雌性大鼠对葡萄糖的耐受性比HSD雄性大鼠更差。我们的观察结果表明，胰岛素抵抗机制包括HSD雄性和雌性组中磷酸化AKT（S473）形式增加，以及HSD雄性组胰腺周围脂肪组织中磷酸化P70S6K1（T389）减少。而在性腺脂肪组织中，HSD雌性大鼠的AKT磷酸化形式减少，但HSD雄性大鼠未减少。最后，HSD组腓肠肌中p-AKT水平降低。
高蔗糖饮食以性别相关差异和组织特异性方式诱导MS和胰岛素抵抗。
