Diet-Induced Metabolic Dysfunction of Hypothalamic Nutrient Sensing in Rodents

International Journal of Molecular Sciences

卷:23

Isabel Arrieta-Cruz¹  Roger Gutiérrez-Juárez²  Hilda Martínez-Coria³  Héctor Eduardo López-Valdés³  Blanca Samara Torres-Ávila⁴ 

[1] Department of Basic Research, National Institute of Geriatrics, Ministry of Health, Mexico City 10200, Mexico;

[2] Department of Biomedical Sciences, School of Medicine, Faculty of Higher Studies Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico;

[3] Department of Physiology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico;

[4] Social Service Program, School of Medicine, Faculty of Higher Studies Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico;

关键词: nutrients;    amino acids;    mediobasal hypothalamus;    glycemia;    liver;    high-fat diet;   

DOI  :  10.3390/ijms23073958

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown