Andalusian Center of Molecular Biology and Regenerative Medicine, CABIMER, University Pablo Olavide, University of Seville, CSIC, Seville, Spain; Biomedical Research Network on Diabetes and Related Metabolic Diseases, CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain.
Andalusian Center of Molecular Biology and Regenerative Medicine, CABIMER, University Pablo Olavide, University of Seville, CSIC, Seville, Spain; Biomedical Research Network on Diabetes and Related Metabolic Diseases, CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain.
Adv Food Nutr Res. 2023;105:173-219. doi: 10.1016/bs.afnr.2022.11.004. Epub 2023 Jan 2.
Lipids play a fundamental role, both structurally and functionally, for the correct functioning of the organism. In the last two decades, they have evolved from molecules involved only in energy storage to compounds that play an important role as components of cell membranes and signaling molecules that regulate cell homeostasis. For this reason, their interest as compounds involved in human health has been gaining weight. Indeed, lipids derived from dietary sources and endogenous biosynthesis are relevant for the pathophysiology of numerous diseases. There exist pathological conditions that are characterized by alterations in lipid metabolism. This is particularly true for metabolic diseases, such as liver steatosis, type 2 diabetes, cancer and cardiovascular diseases. The main issue to be considered is lipid homeostasis. A precise control of fat homeostasis is required for a correct regulation of metabolic pathways and safe and efficient energy storage in adipocytes. When this fails, a deregulation occurs in the maintenance of systemic metabolism. This happens because an increased concentrations of lipids impair cellular homeostasis and disrupt tissue function, giving rise to lipotoxicity. Fat accumulation results in many alterations in the physiology of the affected organs, mainly in metabolic tissues. These alterations include the activation of oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, increased inflammation, accumulation of bioactive molecules and modification of gene expression. In this chapter, we review the main metabolic diseases in which alterations in lipid homeostasis are involved and discuss their pathogenic mechanisms.
脂质在生物体的正常功能中起着结构和功能的基本作用。在过去的二十年中，它们已经从仅参与能量储存的分子演变为在细胞膜成分和调节细胞内稳态的信号分子中发挥重要作用的化合物。因此，它们作为与人类健康相关的化合物的重要性日益增加。事实上，源自饮食来源和内源性生物合成的脂质与许多疾病的病理生理学有关。存在一些以脂质代谢改变为特征的病理状况。这对于代谢疾病，如肝脂肪变性、2 型糖尿病、癌症和心血管疾病尤其如此。需要考虑的主要问题是脂质内稳态。脂肪内稳态的精确控制对于代谢途径的正确调节以及脂肪细胞中安全有效的能量储存是必需的。当这种控制失败时，就会发生全身代谢的失调。这是因为脂质浓度的增加会损害细胞内稳态并破坏组织功能，从而导致脂毒性。脂肪堆积会导致受影响器官的生理发生许多改变，主要是在代谢组织中。这些改变包括氧化应激和内质网应激的激活、线粒体功能障碍、炎症增加、生物活性分子的积累以及基因表达的改变。在本章中，我们回顾了涉及脂质内稳态改变的主要代谢疾病，并讨论了它们的发病机制。
