campest-5-en-3-one and Body-Weight

The effect of dietary 5-campestenone (campest-5-en-3-one), a chemical modification product of a naturally-occurring plant sterol, campesterol, on lipid metabolism was examined using a rat liver perfusion system. Male Sprague-Dawley rats weighing about 140 g were fed a diet supplemented with or without 0.2% 5-campestenone for 14 d. 5-Campestenone feeding resulted in a marked reduction in the concentrations of serum lipids, such as triacylglycerol (TG), cholesterol, phospholipid, and free fatty acid, without influencing food intake or growth. Then, isolated livers from both groups were perfused for 4 h in the presence of an exogenous linoelaidic acid substrate. Dietary 5-campestenone markedly elevated hepatic ketone body production, while cumulative secretions of TG, cholesterol, and phospholipid by the livers of rats fed 5-campestenone were all significantly lowered as compared to those fed without the compound: the extent of the reduction was more prominent in the secretion of TG than other lipid components. In addition, the reduction of TG secretion was concomitantly accompanied by the reduced incorporation of both exogenous and endogenous fatty acids into this lipid molecule. These results suggest that dietary 5-campestenone exerts its hypotriglyceridemic effect, at least, in part through an enhanced metabolism of endogenous and exogenous fatty acids to oxidation at the expense of esterification in rat liver.

Topics: Animal Feed; Animals; Body Weight; Cholestenones; Cholesterol; Eating; Fatty Acids; Lipid Metabolism; Liver; Male; Organ Size; Oxidation-Reduction; Perfusion; Phospholipids; Rats; Rats, Sprague-Dawley; Triglycerides

Dietary campest-5-en-3-one (campestenone), an oxidized derivative of campesterol, significantly reduced visceral fat weight and the concentration of triacylglycerol in serum and liver of rats. Dietary campestenone dramatically increased the activities and the mRNA expressions of mitochondrial and peroxisomal enzymes involved in beta-oxidation in the liver. Campestenone activated human peroxisome proliferator-activated receptor (PPAR) alpha as determined using the novel GAL4 ligand-binding domain chimera assay system with coactivator coexpression. In contrast, dietary campestenone reduced the activities and the mRNA expressions of enzymes involved in fatty acid synthesis, except for the malic enzyme. Dietary campestenone decreased the sterol regulatory element binding protein-1 (SREBP-1) mRNA level. Energy expenditure was significantly higher in the feeding of campestenone in rats. Dietary campestenone reduced hepatic cholesterol concentration and increased fecal excretion of neutral steroids originated from cholesterol. Lymphatic absorption of cholesterol was reduced by the coadministration of campestenone in rats cannulated in the thoracic duct. These observations suggest a possibility that campestenone has an ability to prevent coronary heart disease by improving obesity and abnormality of lipid metabolism.

Topics: Animals; Body Weight; Cholesterol; Energy Metabolism; Fatty Acids; Feces; Intra-Abdominal Fat; Liver; Male; Oxidation-Reduction; Oxidoreductases; Phytosterols; PPAR alpha; Rats; Rats, Inbred Strains; RNA, Messenger; Steroids; Sterol Regulatory Element Binding Protein 1

We examined the therapeutic effects of dietary exposure to 5-campestenone (24-methylcholest-5-en-3-one), an enone derivative of campesterol, in C57BL/KsJ-db/db mice, which are an animal model of obese type 2 diabetes. Blood glucose levels of db/db mice linearly increased from 270 to 720 mg/dl in 10 weeks, an approximately 7-fold difference from the levels of db/+m mice. The 0.3 % dietary exposure to 5-campestenone caused a marked reduction in blood glucose levels of 330 mg/dl after 10 weeks of feeding with a concomitant inhibition of glucose excretion in urine. Only slight efficacy was observed with 0.1 % dietary exposure to this chemical in db/db mice. Significant decreases of plasma triglyceride and plasma free fatty acid were also observed in db/db mice at a 0.3 % dose. However, feed efficiency and body-weight gain in db/db mice was improved by 5-campestenone. No obvious anomaly due to consumption of 5-campestenone was detected by necropsy or clinical observation.

Topics: Animals; Blood Glucose; Body Weight; Cholestenones; Diabetes Mellitus, Type 2; Eating; Female; Glucose Tolerance Test; Glycosuria; Hypoglycemic Agents; Insulin; Lipids; Male; Mice; Mice, Inbred C57BL