Post-ingestive feedbacks and associative learning regulate the intake of unsuitable sterols in a generalist grasshopper.
Behavioural studies of the grasshopper Schistocerca americana were undertaken to identify the mechanisms that regulate the intake of dietary sterols. In the first experiment, grasshoppers were allowed to feed on spinach, a plant containing only unsuitable sterols; immediately after this first meal, a suitable or unsuitable sterol was injected into the haemolymph. Grasshoppers injected with unsuitable sterols had second meals on spinach that were significantly shorter than those of grasshoppers injected with suitable sterols, indicating that unsuitable dietary sterols are detected post-ingestively. In the second experiment, grasshoppers were fed food containing only unsuitable sterols and were then presented with glass-fibre discs containing different concentrations of a suitable sterol or sucrose only (the control). The results suggest that grasshoppers do not use a direct feedback operating on mouthpart chemoreceptors to regulate their intake of suitable sterols. In the third experiment, grasshoppers were presented with artificial diets containing different sterols and flavours, and feeding was observed over a sequence of meals. The results from both the first and last experiments suggest a role for associative learning in regulating the intake of unsuitable sterols. (+info)
The Arabidopsis dwarf1 mutant is defective in the conversion of 24-methylenecholesterol to campesterol in brassinosteroid biosynthesis.
Since the isolation and characterization of dwarf1-1 (dwf1-1) from a T-DNA insertion mutant population, phenotypically similar mutants, including deetiolated2 (det2), constitutive photomorphogenesis and dwarfism (cpd), brassinosteroid insensitive1 (bri1), and dwf4, have been reported to be defective in either the biosynthesis or the perception of brassinosteroids. We present further characterization of dwf1-1 and additional dwf1 alleles. Feeding tests with brassinosteroid-biosynthetic intermediates revealed that dwf1 can be rescued by 22alpha-hydroxycampesterol and downstream intermediates in the brassinosteroid pathway. Analysis of the endogenous levels of brassinosteroid intermediates showed that 24-methylenecholesterol in dwf1 accumulates to 12 times the level of the wild type, whereas the level of campesterol is greatly diminished, indicating that the defective step is in C-24 reduction. Furthermore, the deduced amino acid sequence of DWF1 shows significant similarity to a flavin adenine dinucleotide-binding domain conserved in various oxidoreductases, suggesting an enzymatic role for DWF1. In support of this, 7 of 10 dwf1 mutations directly affected the flavin adenine dinucleotide-binding domain. Our molecular characterization of dwf1 alleles, together with our biochemical data, suggest that the biosynthetic defect in dwf1 results in reduced synthesis of bioactive brassinosteroids, causing dwarfism. (+info)
Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein E-deficient mice: possible mechanisms of action.
BACKGROUND: The effects of probucol and a phytosterol mixture (FCP-3PI) on atherosclerotic lesion formation, plasma lipoproteins, hepatic and lipoprotein lipase activities, antioxidant enzyme activities, and plasma fibrinogen were investigated in apolipoprotein E-knockout (apoE-KO) mice. METHODS AND RESULTS: Three groups of 8 mice were fed a diet containing 9% (wt/wt) fat (controls) or the foregoing diet supplemented with either 1% (wt/wt) probucol (the probucol group) or 2% (wt/wt) FCP-3PI (the FCP-3PI group) for 20 weeks. Compared with controls, atherosclerotic lesion size was 3 times greater in the probucol group, whereas it was decreased by half in the FCP-3PI group. Probucol treatment resulted in high plasma probucol concentrations, which correlated (r=0.69) with the lesion area. HDL cholesterol was reduced (>75%) in the probucol group and slightly increased (14%) in the FCP-3PI-treated group. Postheparin lipoprotein lipase (LPL) activity was significantly reduced in both treatment groups, but only FCP-3PI significantly decreased hepatic lipase activity. Plasma fibrinogen was increased 42% by probucol and decreased 19% by FCP-3PI relative to controls. Probucol significantly increased plasma glutathione reductase, glutathione peroxidase, and superoxide dismutase activities (P<0.05). In contrast to findings in apoE-KO mice, there was no probucol-induced atherosclerosis in their wild-type counterparts fed the same dose for the same period of time. CONCLUSIONS: Antiatherogenic activity of FCP-3PI in apoE-KO mice is associated with an increase in HDL cholesterol concentration along with decreases in hepatic lipase activity and plasma fibrinogen concentrations. Proatherogenic effects of probucol may be related to increased plasma fibrinogen, decreased HDL cholesterol concentrations along with decreased LPL activity, or its direct "toxicity" due to very high plasma concentration. Our studies demonstrate that the antioxidant and cholesterol-lowering properties of probucol do not prevent atherogenesis in this particular animal model. (+info)
Serum sterols during stanol ester feeding in a mildly hypercholesterolemic population.
We investigated the changes of cholesterol and non-cholesterol sterol metabolism during plant stanol ester margarine feeding in 153 hypercholesterolemic subjects. Rapeseed oil (canola oil) margarine without (n = 51) and with (n = 102) stanol (2 or 3 g/day) ester was used for 1 year. Serum sterols were analyzed with gas-liquid chromatography. The latter showed a small increase in sitostanol peak during stanol ester margarine eating. Cholestanol, campesterol, and sitosterol proportions to cholesterol were significantly reduced by 5-39% (P < 0.05 or less for all) by stanol esters; the higher their baseline proportions the higher were their reductions. The precursor sterol proportions were significantly increased by 10- 46%, and their high baseline levels predicted low reduction of serum cholesterol. The decrease of the scheduled stanol dose from 3 to 2 g/day after 6-month feeding increased serum cholesterol by 5% (P < 0. 001) and serum plant sterol proportions by 8-13% (P < 0.001), but had no consistent effect on precursor sterols. In twelve subjects, the 12-month level of LDL cholesterol exceeded that of baseline; the non-cholesterol sterol proportions suggested that stimulated synthesis with relatively weak absorption inhibition contributed to the non-responsiveness of these subjects. In conclusion, plant stanol ester feeding lowers serum cholesterol in about 88% of subjects, decreases the non-cholesterol sterols that reflect cholesterol absorption, increases the sterols that reflect cholesterol synthesis, but also slightly increases serum plant stanols. Low synthesis and high absorption efficiency of cholesterol results in the greatest benefit from stanol ester consumption. (+info)
Cholesterol-lowering efficacy of a sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men.
BACKGROUND: Dietary plant sterols (phytosterols) have been shown to lower plasma lipid concentrations in animals and humans. However, the effect of phytosterol intake from tall oil on cholesterol and phytosterol metabolism has not been assessed in subjects fed precisely controlled diets. OBJECTIVE: Our objective was to examine the effects of sitostanol-containing phytosterols on plasma lipid and phytosterol concentrations and de novo cholesterol synthesis rate in the context of a controlled diet. DESIGN: Thirty-two hypercholesterolemic men were fed either a diet of prepared foods alone or a diet containing 1.7 g phytosterols/d for 30 d in a parallel study design. RESULTS: No overall effects of diet on total cholesterol concentrations were observed, although concentrations were lower with the phytosterol-enriched than with the control diet on day 30 (P < 0.05). LDL-cholesterol concentrations on day 30 had decreased by 8.9% (P < 0.01) and 24.4% (P < 0.001) with the control and phytosterol-enriched diets, respectively. HDL-cholesterol and triacylglycerol concentrations did not change significantly. Moreover, changes in circulating campesterol and beta-sitosterol concentrations were not significantly different between phytosterol-fed and control subjects. In addition, there were no significant differences in fractional (0.091 +/- 0.028 and 0.091 +/- 0.026 pool/d, respectively) or absolute (0.61 +/- 0.24 and 0.65 +/- 0.23 g/d, respectively) synthesis rates of cholesterol observed between control and phytosterol-fed subjects. CONCLUSION: Addition of blended phytosterols to a prudent North American diet improved plasma LDL-cholesterol concentrations by mechanisms that did not result in significant changes in endogenous cholesterol synthesis in hypercholesterolemic men. (+info)
Arabidopsis det2 is defective in the conversion of (24R)-24-methylcholest-4-En-3-one to (24R)-24-methyl-5alpha-cholestan-3-one in brassinosteroid biosynthesis.
Previously, we have shown that the Arabidopsis det2 (deetiolated2) mutant is defective in the biosynthesis of brassinosteroids (BR) and that DET2 (a steroid 5alpha-reductase) acts early in the proposed BR biosynthetic pathway. In this paper we present further biochemical characterization of det2. We have undertaken metabolic experiments with 2H-labeled substrates of intermediates involved in the formation of campestanol from campesterol, and quantitative analysis of intermediates in Arabidopsis wild type and det2. The results of these studies indicate the early operating steps of BR biosynthesis as: campesterol --> 4-en-3beta-ol --> 4-en-3-one --> 3-one --> campestanol in Arabidopsis, with det2 deficient in the conversion of 4-en-3-one to 3-one. We have also detected these intermediates in the formation of campestanol from campesterol and their metabolic conversions using cultured cells of Catharanthus roseus. These studies confirmed the biosynthetic sequence of events from campesterol to campestanol as was found in Arabidopsis. As such, the originally proposed biosynthetic pathway should be modified. (+info)
Hepatitis C: epidemiology and review of complementary/alternative medicine treatments.
Hepatitis C is emerging as a serious worldwide problem. In the United States the current mortality figures may triple in the next ten years, rivaling HIV. The disease has a latency of 10-30 years and symptoms or signs may not appear until cirrhosis is evident. Adequate diagnosis, including liver biopsy, is essential in assessing the current stage of the viral infection and the need for treatment. Hepatitis C may manifest as hepatic fibrosis, cirrhosis, hepatocellular carcinoma, lichen planus, glomerulonephritis, mixed cryoglobulinemia, or porphyria. The hepatic damage is due both to the cytopathic effect of the virus and the inflammatory changes secondary to immune activation. The use of the botanical components glycyrrhizin, catechin, silymarin and phytosterols, and the antioxidants N-acetylcysteine and vitamin E are reviewed for their efficacy in treating chronic hepatitis and affecting liver damage. (+info)
The cholesterol-lowering action of plant stanol esters.
Plant sterols and stanols derived from wood pulp and vegetable oils lower total and LDL cholesterol by inhibiting cholesterol absorption from the intestine in humans. Plant stanols are virtually unabsorbable, which makes them more ideal hypocholesterolemic agents than plant sterols. The esterification of plant stanols has allowed their incorporation into various foods such as margarine without changing the taste and texture of those foods. Plant stanol esters at a level of 2-3 g/d have been shown to reduce LDL cholesterol by 10-15% without side effects. Plant stanol esters appear to be a helpful dietary adjunct to a prudent diet to lower cholesterol. (+info)