Newberne P M
Adv Exp Med Biol. 1986;206:223-51. doi: 10.1007/978-1-4613-1835-4_18.
The lipotropes (choline, methionine, folate, and vitamin B12) have a rich history, with many fluctuations in scientific effort and popularity, covering the past 6 decades. A thin thread of common interest in 1-carbon metabolism and a small band of dedicated individuals have kept this area of biology alive. Today, the lipotropes are enjoying a resurgence of interest and effort with promise for significant contributions to some of our most serious chronic diseases. Between 1920, when Banting and Best initiated a work that led to the discovery of insulin, and 1982-83, when investigators working in 3 laboratories announced that lipotrope deficiency alone could result in liver cancer in rodents, many have used this model to study nutritional problems and, more recently, carcinogenesis. Lipotropes are important to lipid metabolism and to synthesis and maintenance of cellular membranes. When weanling rats were fed a diet low in lipotropes, within a few days the liver accumulated lipid, first in the centrilobular zone and later throughout the entire lobule and lobe. If the diet was continued for a longer period, the liver underwent fibrosis and cirrhosis with some rats ultimately developing hepatocellular carcinoma. Although lipotrope deficiency can result in liver cancer, all hepatocarcinogens tested thus far were enhanced in their activity by diets low in lipotropes. Important changes associated with lipotrope deficiency included membrane damage, decreased serum very low density lipoprotein and drug metabolizing enzymes, decreases in S-adenosylmethionine and in methylation of cytosine, increases in cellular peroxidation products and free radicals, decreased immunocompetence, and a markedly shortened lag time for chemical induction of liver cancer in animals. The overall effect of lipotrope deficiency is an increase in the susceptibility to cancer in animals; the exact mechanisms are unclear.
促脂物质（胆碱、蛋氨酸、叶酸和维生素B12）有着丰富的历史，在过去60年里，对它们的科研投入和关注度波动很大。对一碳代谢的共同兴趣以及一小群专注的个体使这个生物学领域得以延续。如今，促脂物质正重新受到关注和投入研究，有望对一些最严重的慢性疾病做出重大贡献。1920年，班廷和贝斯特开始了一项工作，最终导致胰岛素的发现；1982 - 1983年，三个实验室的研究人员宣布，仅促脂物质缺乏就可能导致啮齿动物患肝癌。在此期间，许多人利用这个模型来研究营养问题，以及最近的致癌作用。促脂物质对脂质代谢以及细胞膜的合成和维持都很重要。当给断奶大鼠喂食促脂物质含量低的饮食时，几天内肝脏就会积累脂质，首先在小叶中心区，随后遍及整个小叶和肝叶。如果持续喂食这种饮食更长时间，肝脏会发生纤维化和肝硬化，一些大鼠最终会发展为肝细胞癌。虽然促脂物质缺乏会导致肝癌，但迄今为止测试的所有肝癌致癌物在促脂物质含量低的饮食作用下其活性都会增强。与促脂物质缺乏相关的重要变化包括膜损伤、血清极低密度脂蛋白和药物代谢酶减少、S - 腺苷甲硫氨酸和胞嘧啶甲基化减少、细胞过氧化产物和自由基增加、免疫能力下降，以及动物化学诱导肝癌的延迟时间明显缩短。促脂物质缺乏的总体影响是增加动物对癌症的易感性；确切机制尚不清楚。
