Antihyperlipidemic and anti-obesity effects of cholesteone

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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.