Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University , Düsseldorf , Germany ; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University , Düsseldorf , Germany ; and German Center of Diabetes Research (DZD e.V.), Munich- Neuherberg , Germany.
Physiol Rev. 2018 Jul 1;98(3):1371-1415. doi: 10.1152/physrev.00015.2017.
Excessive energy intake and reduced energy expenditure drive the development of insulin resistance and metabolic diseases such as obesity and type 2 diabetes mellitus. Metabolic signals derived from dietary intake or secreted from adipose tissue, gut, and liver contribute to energy homeostasis. Recent metabolomic studies identified novel metabolites and enlarged our knowledge on classic metabolites. This review summarizes the evidence of their roles as mediators of interorgan crosstalk and regulators of insulin sensitivity and energy metabolism. Circulating lipids such as free fatty acids, acetate, and palmitoleate from adipose tissue and short-chain fatty acids from the gut effectively act on liver and skeletal muscle. Intracellular lipids such as diacylglycerols and sphingolipids can serve as lipotoxins by directly inhibiting insulin action in muscle and liver. In contrast, fatty acid esters of hydroxy fatty acids have been recently shown to exert a series of beneficial effects. Also, ketoacids are gaining interest as potent modulators of insulin action and mitochondrial function. Finally, branched-chain amino acids not only predict metabolic diseases, but also inhibit insulin signaling. Here, we focus on the metabolic crosstalk in humans, which regulates insulin sensitivity and energy homeostasis in the main insulin-sensitive tissues, skeletal muscle, liver, and adipose tissue.
能量摄入过多和能量消耗减少会导致胰岛素抵抗和代谢疾病的发生，如肥胖和 2 型糖尿病。源自饮食摄入或由脂肪组织、肠道和肝脏分泌的代谢信号有助于维持能量平衡。最近的代谢组学研究确定了新的代谢物，并扩大了我们对经典代谢物的认识。本综述总结了它们作为器官间串扰介质和胰岛素敏感性及能量代谢调节剂的作用证据。来自脂肪组织的循环脂质（如游离脂肪酸、醋酸盐和棕榈油酸）和来自肠道的短链脂肪酸，可有效作用于肝脏和骨骼肌。细胞内脂质（如二酰基甘油和神经鞘脂）可通过直接抑制肌肉和肝脏中的胰岛素作用而成为脂毒性物质。相反，羟基脂肪酸的脂肪酸酯最近被证明具有一系列有益作用。此外，酮酸作为胰岛素作用和线粒体功能的有效调节剂正受到关注。最后，支链氨基酸不仅可以预测代谢疾病，还可以抑制胰岛素信号。在这里，我们专注于人类的代谢串扰，它调节主要胰岛素敏感组织（骨骼肌、肝脏和脂肪组织）的胰岛素敏感性和能量平衡。
