Antihyperlipidemic and anti-obesity effects of cholesteone

我们研究了肠道胆固醇分解代谢的生物学效应，发现0.5%的膳食暴露于胆碱酯-4-烯-3-酮可显著抑制CDFL小鼠体内脂肪的积累，而没有任何厌食和临床异常。Cholesten-3-one的减肥作用在不同物种中也得到了认可。以Wistar和Fischer F344大鼠、Wistar和Fischer F344大鼠为实验对象，分别给高脂血症和肥胖SD大鼠灌胃给予胆甾烯-4-烯-3-酮和胆甾烯-5-烯-3-酮，可显著抑制体重增加和体脂蓄积，显著降低血清胆固醇和甘油三酯水平。我们阐明了胆固酮-3-酮类化合物不仅能显著抑制体重增加和体脂积累，而且能显著抑制血清中胆固醇和甘油三酯的含量，且没有明显的临床异常和厌食现象。化学和生理特性表明，这些类固醇是一类新的抗膳食脂肪吸收药物。需要进一步研究以澄清这些化合物的作用方式，并筛选更有效和毒性更低的化合物。

We studied biological effects of intestinal catabolites of cholesterol, and found that 0.5% dietary exposure to cholest-4-en-3-one markedly inhibited body fat accumulation of CDFl mice without any anorexia and clinical abnormalities. the anti-obesity effect of cholesten-3-one was also recognized in different species. When WHHL rabbits are models of hyperlipidemia, dietary obesity Sprague-Dawley (SD) rats, and normal SD,Wistar and Fischer F344 rats, were administered cholest-4-en-3-one or cholest-5-en-3-one, the animals showed significant inhibition of body weight gain and body fat accumulation as well as marked decrease of serum cholesterol and trygliceride.We noted that chloest-4-en-3-one has an enone structre with a smaller polar carbonyl group at position C3, designed a series of enones and related steroids, and investigated a structure-effect relationship of these steroides to body weight, abdominal fat weight and serum lipid concentration. We clarified that cholesten-3-ones, which possess an enone structure with a carbonyl group at C3, markedly inhibit not only weight gain and body fat accumulation but also the amounts of cholesterol and trygliceride in the serum without any obvious clinical abnormalities and anorexia.Chemical and physiological characters suggest that these steroids are a new class of anti-absorptive agents for dietary fat. Further investigations to clarify the mode of action of these compounds and screening of more effective and less toxic compounds are required.