Except for epidermis and liver, little is known about endogenous expression of 1-O-acylceramides (1-OACs) in mammalian tissue. Therefore, we screened several organs (brain, lung, liver, spleen, lymph nodes, heart, kidney, thymus, small intestine, and colon) from mice for the presence of 1-OACs by LC-MS². In most organs, low levels of about 0.25–1.3 pmol 1-OACs/mg wet weight were recorded. Higher levels were detected in liver, small and large intestines, with about 4–13 pmol 1-OACs/mg wet weight. 1-OACs were esterified mainly with palmitic, stearic, or oleic acids. Esterification with saturated very long-chain fatty acids, as in epidermis, was not observed. Western-type diet induced 3-fold increased 1-OAC levels in mice livers while ceramides were unaltered. In a mouse model of Farber disease with a decrease of acid ceramidase activity, we observed a strong, up to 50-fold increase of 1-OACs in lung, thymus, and spleen. In contrast, 1-OAC levels were reduced 0.54-fold in liver. Only in lung 1-OAC levels correlated to changes in ceramide levels - indicating tissue-specific mechanisms of regulation. Glucosylceramide synthase deficiency in liver did not cause changes in 1-OAC or ceramide levels, whereas increased ceramide levels in glucosylceramide synthase-deficient small intestine caused an increase in 1-OAC levels. Deficiency of Dgat1 in mice resulted in a reduction of 1-OACs to 30% in colon, but not in small intestine and liver, going along with constant free ceramides levels. From these data, we conclude that Dgat1 as well as lysosomal lipid metabolism contribute in vivo to homeostatic 1-OAC levels in an organ-specific manner.

除表皮和肝脏外，对哺乳动物组织中1-O-酰基神经酰胺（1-OAC）的内源表达知之甚少。因此，我们通过LC-MS ²从小鼠中筛选了几种器官（大脑，肺，肝，脾，淋巴结，心脏，肾脏，胸腺，小肠和结肠）中是否存在1-OAC。。在大多数器官中，记录到的低含量约为0.25–1.3 pmol 1-OAC / mg湿重。在肝，小肠和大肠中检测到较高的含量，湿重约为4–13 pmol 1-OAC / mg。1-OAC主要用棕榈酸，硬脂酸或油酸酯化。如在表皮中，未观察到用饱和的超长链脂肪酸酯化。西式饮食在小鼠肝脏中导致1-OAC水平增加3倍，而神经酰胺未改变。在具有酸性神经酰胺酶活性降低的Farber疾病小鼠模型中，我们观察到肺，胸腺和脾脏中1-OAC的增加高达50倍。相反，肝脏中的1-OAC水平降低了0.54倍。仅在肺中1-OAC的水平与神经酰胺水平的变化相关-表明组织的特定调节机制。肝脏中的葡萄糖基神经酰胺合酶缺乏症不会引起1-OAC或神经酰胺水平的改变，而在葡萄糖基神经酰胺合酶缺乏的小肠中神经酰胺水平的升高却导致1-OAC水平的升高。小鼠中Dgat1的缺乏导致结肠中1-OAC含量降低至30％，但在小肠和肝脏中却没有，同时恒定的游离神经酰胺水平也随之降低。从这些数据，我们得出结论，Dgat1以及溶酶体脂质代谢体内以体内特定的方式达到稳态的1-OAC水平。