7-Hydroxymatairesinol (7-HMR) is a plant lignan abundant in various concentrations in plant foods. The objective of this study was to test HMRLignan™, a purified form of 7-HMR, and the corresponding Picea abies extract (total extract P. abies; TEP) as dietary supplements on a background of a high-fat diet (HFD)-induced metabolic syndrome in mice and in the 3T3-L1 adipogenesis model. Mice, 3 weeks old, were fed a HFD for 60 d. Subgroups were treated with 3 mg/kg body weight 7-HMR (HMRLignan™) or 10 mg/kg body weight TEP by oral administration. 7-HMR and TEP limited the increase in body weight (−11 and −13 %) and fat mass (−11 and −18 %) in the HFD-fed mice. Epididymal adipocytes were 19 and −12 % smaller and the liver was less steatotic (−62 and −65 %). Serum lipids decreased in TEP-treated mice (−11 % cholesterol, −23 % LDL and −15 % TAG) and sugar metabolism was ameliorated by both lignan preparations, as shown by a more than 70 % decrease in insulin secretion and insulin resistance. The expression of several metabolic genes was modulated by the HFD with an effect that was reversed by lignan. In 3T3-L1 cells, the 7-HMR metabolites enterolactone (ENL) and enterodiol (END) showed a 40 % inhibition of cell differentiation accompanied by the inhibited expression of the adipogenic genes PPARγ, C/EBPα and aP2. Furthermore, END and ENL caused a 10 % reduction in TAG uptake in HEPA 1–6 hepatoma cells. In conclusion, 7-HMR and TEP reduce metabolic imbalances typical of the metabolic syndrome and obesity in male mice, whereas their metabolites inhibit adipogenesis and lipid uptake in vitro.

Ruminal microbiota plays an important role in the conversion of plant lignans into mammalian lignans. The main mammalian lignan present in the milk of dairy cows fed flax products is enterolactone (EL). The objectives of the present study were to investigate the effects of abomasal infusion of flax oil on the metabolism of flax lignans and concentrations of EL in biological fluids of dairy cows. A total of six rumen-cannulated dairy cows were assigned within a 2 × 3 factorial arrangement of six treatments utilising flax hulls (0 and 15·9 % of DM) and abomasal infusion of flax oil (0, 250 and 500 g/d). There were six periods of 21 d each. Samples were collected during the last 7 d of each period and subjected to chemical analysis. Flax hull supplementation increased concentrations of EL in ruminal fluid, plasma, urine and milk, while flax oil infusion had no effect. Post-feeding, β-glucuronidase activity in the ruminal fluid of cows infused with 250 g flax oil was significantly lower for cows fed hulls than for those fed the control diet. The present study demonstrated that the presence of a rich source of n-3 fatty acids such as flax oil in the small intestine does not interfere with the absorption of the mammalian lignan EL and that lower ruminal β-glucuronidase activity had no effect on the conversion of flax lignans into EL in the rumen of dairy cows.

Elevated C-reactive protein (CRP), IL-6 and retinol-binding protein 4 (RBP4) levels are associated with insulin resistance and diabetes mellitus. Phytoestrogens (including lignans and isoflavones) may enhance the management of diabetes and are hypothesized to act through inflammation pathways. The present study explored the effects of flaxseed-derived lignan on inflammatory factors and RBP4 concentrations in type 2 diabetics, who have higher levels of these biomarkers. Seventy community-dwelling diabetic patients (twenty-six men and forty-four post-menopausal women) with mild hypercholesterolaemia completed a randomized, double-blind, placebo-controlled, cross-over trial of supplementation with flaxseed-derived lignan capsules (360 mg/d) or placebo for 12 weeks, separated by an 8-week wash-out period. The participants maintained their habitual diets and levels of physical activity. Baseline to follow-up concentrations of CRP increased significantly within the placebo group (1·42 (sem 0·19) v. 1·96 (sem 0·22) mg/l, P < 0·001), but were comparatively unchanged in the lignan-supplemented group (1·67 (sem 0·19) v. 1·90 (sem 0·26) mg/l, P = 0·94); a significant difference was observed between treatments ( − 0·45 (95 % CI − 0·76, − 0·08) mg/l, P = 0·021). This effect was confined to women (P = 0·016), but not observed in men (P = 0·49). No between-treatment differences were found with regard to IL-6 or RBP4; though IL-6 concentrations increased significantly from baseline to follow-up in both groups (P = 0·004 and P < 0·001 following lignan and placebo treatments, respectively). The study suggests that lignan might modulate CRP levels in type 2 diabetics. These results need to be confirmed by further large clinical trials of longer duration.

Flaxseed lignan secoisolariciresinol diglucoside (SDG) has been reported to prevent and alleviate lifestyle-related diseases including diabetes and hypercholesterolaemic atherosclerosis. This study assesses the effect of SDG on the development of diet-induced obesity in mice and the effect of the SDG metabolite enterodiol (END) on adipogenesis in 3T3-L1 adipocytes. We compared body weight, visceral fat weight, liver fat content, serum parameters, mRNA levels of lipid metabolism-related enzymes and adiponectin in mice fed either a low-fat diet (5 % TAG), high-fat diet (30 % TAG) or high-fat diet containing 0·5 and 1·0 % (w/w) SDG for 4 weeks. Administration of SDG to mice significantly reduced high-fat diet-induced visceral and liver fat accumulation, hyperlipaemia, hypercholesterolaemia, hyperinsulinaemia and hyperleptinaemia. SDG also suppressed sterol regulatory element binding protein 1c mRNA level in the liver and induced increases in the adiponectin mRNA level in the white adipose tissue and carnitine palmitoyltransferase I mRNA level in the skeletal muscle. Differentiated 3T3-L1 adipocytes were treated with 0, 5, 10 and 20 μmol/l END and then assayed for mRNA expression of adipogenesis-related genes and DNA binding activity of PPARγ to the PPAR response element consensus sequence. END induced adipogenesis-related gene mRNA expression including adiponectin, leptin, glucose transporter 4 and PPARγ, and induced PPARγ DNA binding activity in 3T3-L1 adipocytes. In conclusion, SDG induced adiponectin mRNA expression and showed beneficial effects on lipid metabolism in diet-induced obesity in mice. Flaxseed lignans are suggested to regulate adipogenesis-related gene expressions through an increase in PPARγ DNA binding activity.

Due to the potential oestrogenic effects of secoisolariciresinol diglycoside (SDG), the mammalian lignan precursor in flaxseed (Linum usitatissimum), we hypothesized that exposure to purified SDG during early life would have a positive effect on developing bone. This present study determined whether exposure to SDG purified from flaxseed during suckling via mother's milk or continuously to adolescence (postnatal day (PND) 50) or adulthood (PND 132) increased bone mineral content (BMC) or bone strength in female rat offspring. Offspring were exposed to basal diet (BD) or one of two doses of SDG (50S, 100S) equivalent to that in a 50 or 100 g flaxseed/kg diet during lactation only or through to PND 50 or 132. At PND 50 and 132, femurs were analysed for BMC by dual energy X-ray absorptiometry and biomechanical strength by a 3-point bending test. Compared with BD group, rats exposed to continuous 50S or 100S diet had stronger femurs at PND 50 without changes in BMC. At PND 132 there were no differences in femur strength despite the fact that continuous exposure to BD resulted in a higher (P<0·05) BMC than rats exposed to 100S during lactation only or to 50S or 100S during lactation through to adulthood. In conclusion, female rat bone is more sensitive to the oestrogen-like action of lignans during early life when endogenous levels of sex hormones are low, but by adulthood the improved bone strength does not persist. Importantly, exposure to purified lignan does not have negative effects on bone strength.