Antihyperlipidemic and anti-obesity effects of cholesteone

我们研究了肠道胆固醇分解代谢物的生物学效应，发现0.5%的饮食暴露于胆固醇-4-en-3-one可显著抑制CDFl小鼠的体脂积累，且无任何厌食症和临床异常。在不同的物种中也发现了胆固醇-3- 1的抗肥胖作用。当WHHL兔作为高脂血症、饮食性肥胖模型时，SD大鼠和正常SD、Wistar和Fischer F344大鼠分别给予胆-4-en-3- 1或胆-5-en-3- 1，动物体重增加和体脂积累明显受到抑制，血清胆固醇和甘油三酯含量明显降低。我们注意到绿-4-烯-3-酮具有一个在C3位置具有较小极性羰基的烯酮结构，设计了一系列烯酮和相关类固醇，并研究了这些类固醇与体重、腹部脂肪重量和血脂浓度的结构-效应关系。我们发现，具有烯酮结构且羰基位于C3的胆甾-3- 1不仅能显著抑制体重增加和体脂积累，还能显著抑制血清中胆固醇和trygliceride的含量，而无明显的临床异常和厌食症。化学和生理特性表明这些类固醇是一类新的膳食脂肪抗吸收剂。需要进一步研究以阐明这些化合物的作用方式，并筛选更有效和毒性更小的化合物。

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.