desmosterol and Body-Weight

Coronary patients with low baseline ratios of serum cholestanol and plant sterols to cholesterol (indicating low cholesterol absorption) but not those with high ratios (high absorption) experienced reduced recurrences of coronary events during simvastatin treatment in the Scandinavian Simvastatin Survival Study. Thus, in the present study, serum cholesterol, its precursor sterols (reflecting cholesterol synthesis), plant sterols (campesterol and sitosterol), and cholestanol were measured before and during a 5-year period of placebo treatment (n=433) and simvastatin treatment (n=434) in patients from a subgroup of the Scandinavian Simvastatin Survival Study to determine whether changes in cholesterol synthesis and serum levels were related to cholesterol absorption. Serum cholesterol level was unchanged, the ratios of cholesterol precursor sterols to cholesterol were decreased, and the ratios of plant sterols to cholesterol were increased in relation to increasing baseline ratios of cholestanol quartiles. The latter predicted 5-year ratios and simvastatin-induced reductions of the precursor sterols, with the lowering of the ratios (cholesterol synthesis reduction) being almost twice higher in the lowest versus the highest quartile. The ratios of plant sterols, especially campesterol, to cholesterol were markedly increased during simvastatin treatment, mostly in subjects with the highest baseline cholestanol quartiles. Simvastatin reduced serum cholesterol more (P=0.003) in the lowest versus the highest cholestanol quartile during the 5-year treatment period. The results show for the first time that baseline cholesterol metabolism, measured by serum noncholesterol sterols, predicts the effectiveness of simvastatin in reducing cholesterol synthesis and serum levels of cholesterol. The drug suppresses the synthesis of cholesterol markedly more effectively in subjects with high than with low baseline synthesis but reduces respective serum cholesterol levels less markedly than synthesis. Subjects with high cholesterol absorption and low synthesis may need a combination therapy to lower more effectively their serum cholesterol levels and prevent an increase in the levels of plant sterols.

Topics: Anticholesteremic Agents; Body Weight; Cholestanol; Cholesterol; Coronary Disease; Desmosterol; Humans; Phytosterols; Placebos; Simvastatin; Sitosterols; Sterols

Lipoprotein distribution of non-cholesterol sterols was studied to evaluate in which lipoproteins they are carried in type 2 diabetes with body weight ranging from normal to overweight.. Serum and lipoprotein squalene and non-cholesterol sterols were quantitated with gas-liquid chromatography in 33 diabetic subjects separated into normal (BMI < or = 25 kg/m2, n=10) and overweight (BMI > 25 kg/m2, n=23) groups.. Two-thirds of the non-cholesterol sterols were carried in LDL and one-fifth in HDL, whereas squalene was mainly in VLDL and LDL in both groups. In overweight versus normal weight subjects, the absorption marker concentrations and ratios to cholesterol in serum and lipoproteins were lower and those of synthesis higher. In both groups the synthesis and absorption markers were interrelated in all lipoproteins suggesting intact regulation of cholesterol metabolism. The absorption marker ratios to cholesterol were mostly carried in HDL (cholestanol) and IDL (campesterol and sitosterol), and synthesis markers in VLDL and IDL regardless of overweight. Synthesis marker ratios were underestimated in serum versus VLDL and IDL, and those of absorption markers in serum versus IDL and HDL (p<0.05 for all). Squalene was related to lathosterol in all lipoprotein fractions (e.g., in LDL r=+0.501, p<0.01) suggesting that in diabetes squalene, too, is an indicator of cholesterol synthesis.. The absorption sterols are carried in IDL and HDL, and the synthesis markers in VLDL and IDL regardless of weight. The lipoprotein squalene and non-cholesterol sterol ratios were under- or overestimated in serum, and whether their evaluation in lipoproteins versus in serum only gives better information on cholesterol metabolism should be investigated further also in normal population.

Topics: Body Weight; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Desmosterol; Diabetes Mellitus, Type 2; Female; Humans; Lipoproteins; Male; Middle Aged; Overweight; Squalene

Topics: Amines; Animals; Anticholesteremic Agents; Azasteroids; Body Weight; Cholestanes; Cholesterol; Desmosterol; Fatty Acids; Feces; Lipids; Liver; Organ Size; Oxidoreductases; Rats; Steroids, Heterocyclic

20,25-Diazacholesterol, known to induce myotonia in skeletal muscle, also affects cardiac muscle as can be concluded from the development of cardiomegaly. At the same time (Na+, K+) ATPase of cardiac sarcolemmal membranes of the 20,25-diazacholesterol treated rats showed an increased activity as compared with control animals (91 percent and 46 percent stimulation respectively). The Ca++ stimulated ATPase showed the same tendency (96 percent and 64 percent stimulation). In the plasma of the treated rats creatine phosphokinase activity was found to be elevated whereas the amount of protein-bound iodine was decreased, a finding that is common in myotonic dystrophy.

Topics: Adenosine Triphosphatases; Animals; Aza Compounds; Biological Transport; Body Weight; Cardiomegaly; Cholesterol; Desmosterol; Female; Myocardium; Myotonia; Organ Size; Rats; Sarcolemma

Topics: Aging; Animals; Body Weight; Cholesterol; Chromatography, Thin Layer; Desmosterol; Palaemonidae; Time Factors

Topics: Animals; Anticholesteremic Agents; Body Weight; Cholesterol; Desmosterol; Estrone; Hypercholesterolemia; Liver; Male; Organ Size; Rats; Triparanol

Topics: Amines; Animals; Body Weight; Carbon Radioisotopes; Cholesterol; Desmosterol; Diet; Hydroxylation; Liver; Male; Organ Size; Oxidation-Reduction; Rats