lignans and Weight-Gain

Brown adipose tissue (BAT) is the site of non-shivering thermogenesis in mammals, wherein energy is dissipated as heat. We observed that aqueous extract of black sesame seed triggers an increase in the expression of Uncoupling Protein 1 (UCP1) in brown adipocytes from mice. The active component from the extract was purified and identified to be sesaminol diglucoside (SDG). SDG treatment decreased mass of white fat pads and serum glucose levels and increased UCP1 levels in BAT thereby protecting mice against high fat induced weight gain. Further in silico and in vitro studies revealed that these effects are due to the agonist like behaviour of SDG towards beta 3 adrenergic receptors (β3-AR). Together, our results suggest that SDG induces BAT mediated thermogenesis through β3-AR and protects mice against diet-induced obesity.

Topics: Adipocytes, Brown; Adipose Tissue, Brown; Animals; Diet, High-Fat; Dioxoles; Furans; Lignans; Lipids; Mice, Inbred C57BL; Plant Extracts; Receptors, Adrenergic, beta-3; Seeds; Sesamum; Thermogenesis; Uncoupling Protein 1; Weight Gain

Consumption of diet rich in lignans may decrease the risk of some chronic hormonal conditions such as benign prostatic hyperplasia (BPH). This study investigated whether a lignan-rich extract from flaxseed hulls, LinumLife EXTRA (LLE), could prevent BPH using the testosterone propionate (TP)-induced BPH rat model. Male Wistar-Unilever rats were randomly divided into four groups of 12 rats each: a negative control group fed with control diet and receiving daily subcutaneous injections of corn oil without TP, and three groups fed with control diet (positive control), diet containing 0.5% LLE (LLE 0.5) or 1.0% LLE (LLE 1.0) and receiving daily subcutaneous injections of TP in corn oil. Treatments with diets started 2 weeks before the induction of BPH and were carried out for 5 consecutive weeks. The influence of TP and LLE on body weight (BW), food and water consumptions, and enterolactone (ENL) levels in serum and urine of rats was examined at the end of the 5-week treatment period. TP significantly diminished the mean body weight gain (MBWG) of positive control rats and their food and water consumptions while LLE reduced significantly this MBWG reduction in a dose-dependent manner. The lignan-rich extract significantly inhibited TP-induced prostate size ratio (prostate weight/rat BW) increase in comparison with positive controls (P<.001). This effect was dose dependent. Higher serum and urine levels of ENL correlated well with the dose of extract provided to rats. It was concluded that the lignan-rich flaxseed hull extract prevented the TP-induced BPH indicating it might be beneficial in the prevention of BPH.

Topics: 4-Butyrolactone; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Drinking; Energy Intake; Flax; Hyperplasia; Lignans; Male; Phytotherapy; Plant Extracts; Prostate; Prostatic Hyperplasia; Rats, Wistar; Seeds; Testosterone Propionate; Weight Gain

Dietary sesamin (1:1 mixture of sesamin and episesamin) decreases fatty acid synthesis but increases fatty acid oxidation in rat liver. Dietary α-lipoic acid lowers hepatic fatty acid synthesis. These changes can account for the serum lipid-lowering effect of sesamin and α-lipoic acid. It is expected that the combination of these compounds in the diet potentially ameliorates lipid metabolism more than the individual compounds. We therefore studied the combined effect of sesamin and α-lipoic acid on lipid metabolism in rats.. Male Sprague-Dawley rats were fed diets supplemented with 0 or 2 g/kg sesamin and containing 0 or 2.5 g/kg α-lipoic acid for 22 days.. Sesamin and α-lipoic acid decreased serum lipid concentrations and the combination of these compounds further decreased the parameters in an additive fashion. These compounds reduced the hepatic concentration of triacylglycerol, the lignan being less effective in decreasing this value. The combination failed to cause a stronger decrease in hepatic triacylglycerol concentration. The combination of sesamin and α-lipoic acid decreased the activity and mRNA levels of hepatic lipogenic enzymes in an additive fashion. Sesamin strongly increased the parameters of hepatic fatty acid oxidation enzymes. α-Lipoic acid antagonized the stimulating effect of sesamin of fatty acid oxidation through reductions in the activity of some fatty acid oxidation enzymes and carnitine concentration in the liver. This may account for the failure to observe strong reductions in hepatic triacylglycerol concentration in rats given a diet containing both sesamin and α-lipoic acid.

Topics: Animals; Appetite Depressants; Carnitine; Dietary Supplements; Dioxoles; Fatty Acids; Gene Expression Regulation, Enzymologic; Hypolipidemic Agents; Lignans; Lipid Metabolism; Lipogenesis; Lipolysis; Liver; Male; Organ Size; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thioctic Acid; Triglycerides; Weight Gain

Flaxseed lignan, secoisolariciresinol has been reported to possess health benefits. We previously synthesized each stereoisomer of secoisolariciresinol and found that (-)-secoisolariciresinol reduces lipid accumulation and induces adiponectin production in 3T3-L1 adipocytes. Here we show the effects of (-)-secoisolariciresinol on high-fat diet-induced obesity in C57BL/6 male mice. Oral administration of (-)-secoisolariciresinol for 28 consecutive days significantly suppressed the gain of body weight. Increased serum adiponectin level and decreased gene expression of fatty acid synthase and sterol regulatory element-binding protein-1c in liver, which are related to fatty acid synthesis, were observed in the mice orally administered with (-)-secoisolariciresinol. In addition, subcutaneous injection of (-)-secoisolariciresinol also significantly suppressed the gain of body weight. Serum leptin levels were significantly increased by treating with (-)-secoisolariciresinol or (-)-enterolactone. Subcutaneous injection of (-)-secoisolariciresinol, (-)-enterolactone, or (-)-enterodiol promoted gene expression of acyl-CoA oxidase, carnitine palmitoyl transferase-1, and peroxisome proliferator-activated receptor α, which are related to β-oxidation. Overall results suggest that (-)-secoisolariciresinol exerts a suppressive effect on the gain of body weight of mice fed a high-fat diet by inducing gene expression of adiponectin, resulting in the altered expression of various genes related to the synthesis and β-oxidation of fatty acids.

Topics: Animals; Butylene Glycols; Diet, High-Fat; Dietary Fats; Disease Models, Animal; Gene Expression; Humans; Lignans; Male; Mice; Mice, Inbred C57BL; Obesity; PPAR alpha; Weight Gain

Honokiol has shown chemopreventive effects in chemically-induced and UVB-induced skin cancer in mice. In this investigation, we assessed the time-effects of a topical low dose of honokiol (30 μg), and then the effects of different honokiol doses (30, 45, and 60 μg) on a UVB-induced skin cancer model to find an optimal dose and time for desirable chemopreventive effects. UVB radiation (30 mJ/cm(2), 5 days/week for 25 or 27 weeks) was used to induce skin carcinogenesis in SKH-1 mice. For the time-response experiment 30 μg honokiol in acetone was applied topically to the animals before the UVB exposure (30 min, 1 h, and 2 h) and after the UVB exposure (immediately, 30 min, and 1 h). Control groups were treated with acetone. For the dose-response study, animals were treated topically with acetone or honokiol (30, 45, and 60 μg) one hour before the UVB exposure. In the time-response experiment, honokiol inhibited skin tumor multiplicity by 49-58% while reducing tumor volumes by 70-89%. In the dose-response study, honokiol (30, 45, and 60 μg) significantly decreased skin tumor multiplicity by 36-78% in a dose-dependent manner, while tumor area was reduced by 76-94%. Honokiol (60 μg) significantly reduced tumor incidence by 40% as compared to control group. Honokiol applied in very low doses (30 μg) either before or after UVB radiation shows chemopreventive effects. Honokiol (30, 45, and 60 μg) prevents UVB-induced skin cancer in a dose-dependent manner. Honokiol can be an effective chemopreventive agent against skin cancer.

Topics: Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Female; Lignans; Mice; Mice, Hairless; Neoplasms, Radiation-Induced; Skin Neoplasms; Tumor Burden; Ultraviolet Rays; Weight Gain

Dietary phytoestrogens, such as the lignan metabolite enterolactone (ENL) and the isoflavone genistein (GEN), are suggested to modulate the risk of estrogen-dependent disease (e.g., breast cancer) through regulation of estrogen signaling. However, the effects of complex food items containing lignans or isoflavones on estrogen receptor (ER) transactivation have not been assessed so far. In this study, the modulation of ER-mediated signaling by dietary sources of lignans (cereals and flaxseed) and isoflavones (soy) was studied in vivo. Adult ovariectomized 3 x ERE-luciferase (luc) reporter mice received isocaloric diets supplemented with flaxseed, rye, wheat, or soy for 40 h or two weeks, and an additional group of mice was challenged with 17beta-estradiol (E(2)) following the two-week dietary intervention. In non-E(2)-treated mice, soy diet induced luc expression in liver, mammary gland, and pituitary gland while the other diets had no effects. Interestingly, all diets modulated the E(2)-induced luc expression. In particular rye diet efficiently reduced E(2)-induced luc expression as well as uterine growth, the hallmark of estrogen action in vivo. It is concluded that dietary sources of lignans and isoflavones can modulate estrogen signaling in vivo. The results suggest intriguing possibilities for the modulation of the risk of estrogen-dependent diseases by dietary means.

Topics: Animals; Diet; Edible Grain; Estradiol; Female; Flax; Isoflavones; Lignans; Luciferases; Mice; Receptors, Estrogen; Weight Gain

We previously demonstrated that the crude acetone extract of Bupleurum scorzonerifolium (BS-AE) 60 microg/ml has anti-proliferation activity and apoptotic effects on A549 non-small cell lung cancer (NSCLC). A novel lignan, isochaihulactone (4-benzo[1,3]dioxol-5-ylmethyl-3(3,4,5-trimethoxyl-benzylidene)-dihydro-furan-2-one), was isolated from BS-AE and identified from spectral evidence ((1)H NMR, (13)C NMR, IR, and MS) and by comparison with authentic synthetic standards. Isochaihulactone was cytotoxic (IC(50)=10-50 microM) in a variety of human tumor cell lines. In in vitro and in vivo microtubule assembly assays, it inhibited tubulin polymerization in a concentration-dependent manner. As determined by flow cytometry, isochaihulactone caused G2/M phase arrest and apoptosis in a time- and concentration-dependent manner. G2/M arrest was correlated with increased p21/WAF1 levels, downregulation of the checkpoint proteins cyclin B1/cdc2 and mobility shift of cdc25C. Moreover, isochaihulactone (30 and 50 mg/kg) inhibited the growth of non-small cell lung carcinoma A549 xenograft in nude mice. These findings indicate isochaihulactone is a promising new antimitotic anticancer compound with potential for clinical application in the future.

Topics: 4-Butyrolactone; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Benzodioxoles; Bupleurum; Cell Line, Tumor; Cell Proliferation; Cell Shape; Dose-Response Relationship, Drug; G2 Phase; Humans; Inhibitory Concentration 50; Lignans; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Fluorescence; Microtubules; Phosphorylation; Plant Extracts; Plant Roots; Tubulin; Weight Gain; Xenograft Model Antitumor Assays

Sesamin, a major lignan from sesame seeds has been associated with cholesterol reduction in previous reports, but recent studies suggested differences in the response to sesamin intake depending on the model studied as well as the nature of the sesamin preparation used.. The effect of pure sesamin epimer on serum lipids was studied in hypercholesterolemic LDL receptor-knockout mice under cholesterol fed condition.. Animals were randomly assigned to 4 groups, fed an atherogenic diet containing stanol ester, sesamin, combination of stanol ester and sesamin or a control diet with no additions.. The control group showed an almost 3-fold increase in serum cholesterol levels due to the atherogenic diet but no effect was seen for triglyceride levels. Stanol ester alone or together with sesamin significantly attenuated the elevation of the cholesterol levels.. Sesamin alone did not affect the elevation of the diet-induced cholesterol level and it did not enhance the effect of stanol ester.

Topics: Animals; Anticholesteremic Agents; Cholesterol; Cholesterol, LDL; Diet, Atherogenic; Dioxoles; Female; Lignans; Mice; Mice, Inbred Strains; Random Allocation; Receptors, LDL; Specific Pathogen-Free Organisms; Triglycerides; Weight Gain

Flaxseed is a dietary source of possible chemopreventive compounds such as lignans and alpha-linolenic acid (ALA). To study the effects of a flaxseed mixture on adenoma formation in multiple intestinal neoplasia mice, the mice were fed a diet containing 2.7 % flaxseed, 4.5 % fibre and 3.7 % ALA. To elucidate the effect of oils of the mixture we also composed a diet without flaxseed but with the same oil composition. The median number of adenomas in the small intestine was fifty-four for the control group, and thirty-seven (P=0.023) and forty-two (P=0.095) for flaxseed and oil groups, respectively. Compared with controls (1.2 mm), the adenoma size was smaller in the flaxseed (0.9 mm; P=0.002) and oil (1.0 mm; P=0.012) groups. Both diets changed the proportions of n-3 and n-6 fatty acids in the colonic mucosa. Membrane beta-catenin and protein kinase C (PKC)-zeta levels were reduced in the adenoma v. mucosa (P<0.05), and an inverse association was found between the membrane PKC-zeta in the mucosa and the adenoma number (r -0.460, P=0.008, n 32). Only the flaxseed diet increased lignan levels in the caecum (P=0.002) and in plasma (P=0.002) but they were not associated with tumour formation. The results suggest that the preventive effect of flaxseed on colon carcinogenesis may be due to the oil part of flaxseed, and the loss of beta-catenin and PKC-zeta from the membranes of the mucosal tissue may play a permissive role in intestinal tumour development.

Topics: Actins; Adenoma; alpha-Linolenic Acid; Animals; beta Catenin; Blotting, Western; Colon; Cyclooxygenase 2; Fatty Acids; Flax; Intestinal Mucosa; Intestinal Neoplasms; Lignans; Linseed Oil; Mice; Mice, Mutant Strains; Models, Animal; Neoplasms, Multiple Primary; Plant Oils; Protein Kinase C; Weight Gain

The effects of a combination of dietary conjugated linoleic acid (CLA) supplemented with sesamin on hepatic ketogenesis and triacylglycerol secretion were compared using the livers of rats fed diets containing 1% CLA or linoleic acid (LA) in combination with 0.2% sesamin for 14 d, respectively. The feeding of CLA, as compared to LA, caused a significant reduction in the weight of perirenal adipose tissue but not that of epididymal adipose tissue, and affected neither growth parameters nor hepatic lipid concentration. Hepatic production of ketone bodies was consistently higher in rats fed CLA than in those fed LA, while triacylglycerol secretion was reversed. No significant difference was noted in the hepatic secretion of cholesterol among the groups. Although there was no effect of the dietary combination of CLA with sesamin on adipose tissue weight, hepatic lipid parameters and ketone body production were observed: i.e., triacylglycerol secretion tended to be reduced. These results suggest that the dietary combination of CLA with sesamin may be an effective approach for lowering serum triacylglycerol levels. The decreased hepatic secretion of triacylglycerol is, in part, due to enhanced fatty acid oxidation in the liver.

Topics: Animals; Anticholesteremic Agents; Body Composition; Diet; Dioxoles; Ketone Bodies; Lignans; Linoleic Acid; Lipid Metabolism; Liver; Male; Perfusion; Rats; Rats, Sprague-Dawley; Time Factors; Triglycerides; Weight Gain

The effect of alpha-tocopherol on the hypocholesterolemic action of sesamin was examined in rats given a cholesterol-enriched diet. When different levels (0.05 and 0.2%) of sesamin were fed, the supplementation of 1% alpha-tocopherol significantly accentuated the hypocholesterolemic action of sesamin, particularly with the higher sesamin level, although alpha-tocopherol alone did not affect the concentration of serum cholesterol. The dose-dependent promoting effect of alpha-tocopherol on the hypocholesterolemic action of sesamin was confirmed by supplementing different levels (0.2 and 1%) of alpha-tocopherol to a fixed level of sesamin (0.2%). alpha-Tocopherol was still effective at the 0.2% level. The metabolism of sesamin in the liver S9 fraction appeared to be interfered with alpha-tocopherol in vitro, suggesting a possible role of alpha-tocopherol in maintenance of the availability of sesamin.

Topics: Animals; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Dioxoles; Drug Interactions; Lignans; Liver; Male; Organ Size; Rats; Rats, Wistar; Vitamin E; Weight Gain

Since lignans have been suggested to have some cancer-protective effects, flaxseed, the most abundant source of lignan precursors, was tested for its effect on early markers of risk for mammary carcinogenesis. Supplementation of a high-fat diet with flaxseed flour (FF) or defatted flaxseed meal (FM) (5% or 10%) reduced the epithelial cell proliferation by 38.8-55.4% and nuclear aberrations by 58.8-65.9% in female rat mammary gland, with optimum effects seen with the 5% FF. These protective effects were accompanied by increases in urinary lignan excretion indicating that they may be related to the ability of flaxseed to provide lignan precursors.

Topics: Animals; Antineoplastic Agents, Phytogenic; Biomarkers, Tumor; Cell Division; Dose-Response Relationship, Drug; Epithelium; Female; Lignans; Lignin; Mammary Neoplasms, Animal; Mutation; Rats; Rats, Inbred Strains; Regression Analysis; Weight Gain