Department of Basic Research, National Institute of Geriatrics, Ministry of Health, Mexico City 10200, Mexico.
Social Service Program, School of Medicine, Faculty of Higher Studies Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico.
Int J Mol Sci. 2022 Apr 2;23(7):3958. doi: 10.3390/ijms23073958.
A sedentary lifestyle and excessive nutrient intake resulting from the consumption of high-fat and calorie-rich diets are environmental factors contributing to the rapid growth of the current pandemic of type 2 diabetes mellitus (DM2). Fasting hyperglycemia, an established hallmark of DM2, is caused by excessive production of glucose by the liver, resulting in the inability of insulin to suppress endogenous glucose production. To prevent inappropriate elevations of circulating glucose resulting from changes in nutrient availability, mammals rely on complex mechanisms for continuously detecting these changes and to respond to them with metabolic adaptations designed to modulate glucose output. The mediobasal hypothalamus (MBH) is the key center where nutritional cues are detected and appropriate modulatory responses are integrated. However, certain environmental factors may have a negative impact on these adaptive responses. For example, consumption of a diet enriched in saturated fat in rodents resulted in the development of a metabolic defect that attenuated these nutrient sensing mechanisms, rendering the animals prone to developing hyperglycemia. Thus, high-fat feeding leads to a state of "metabolic disability" in which animals' glucoregulatory responses fail. We postulate that the chronic faltering of the hypothalamic glucoregulatory mechanisms contributes to the development of metabolic disease.
久坐的生活方式和高脂肪、高热量饮食导致的过度营养摄入，是导致当前 2 型糖尿病（DM2）迅速流行的环境因素。空腹高血糖是 DM2 的一个既定标志，是由肝脏过度产生葡萄糖引起的，导致胰岛素无法抑制内源性葡萄糖生成。为了防止由于营养物质可用性的变化而导致循环葡萄糖的不当升高，哺乳动物依赖于复杂的机制来持续检测这些变化，并通过旨在调节葡萄糖输出的代谢适应来对其做出反应。中脑腹侧下丘脑（MBH）是检测营养线索和整合适当调节反应的关键中心。然而，某些环境因素可能对这些适应性反应产生负面影响。例如，在啮齿动物中摄入富含饱和脂肪的饮食会导致代谢缺陷的发展，从而削弱这些营养感应机制，使动物容易发生高血糖。因此，高脂肪喂养会导致动物的糖调节反应失败的“代谢障碍”状态。我们假设下丘脑糖调节机制的慢性衰竭导致代谢疾病的发展。
