hydroxymatairesinol and Body-Weight

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.

Topics: 3T3-L1 Cells; 4-Butyrolactone; Adipogenesis; Adipose Tissue; Animals; Anti-Obesity Agents; Blood Glucose; Body Weight; Diet, High-Fat; Dietary Supplements; Fatty Liver; Gene Expression; Insulin Resistance; Lignans; Lipid Metabolism; Lipids; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Picea; Plant Extracts

Plant lignan 7-hydroxymatairesinol (7-HMR) is a novel precursor of the mammalian lignan enterolactone. A 13 week toxicity study at dietary levels of 0, 0.25, 1, and 4% (w/w) of potassium acetate complex of 7-HMR (HMRlignan) was conducted in the Wistar rat. These dietary levels resulted in an average daily intake of 160, 640, and 2600 mg HMRlignan/kg body weight/day, respectively. A considerable systemic exposure of HMRlignan was verified by dose-related increases in plasma total (conjugated and unconjugated) concentration of 7-HMR and metabolites enterolactone, 7-hydroxyenterolactone, and matairesinol. Enterolactone appeared to be the major metabolite. Most (>96%) of the circulating 7-HMR and enterolactone was in conjugated form as measured from the low-dose rat plasma samples. HMRlignan exposure did not significantly affect clinical signs, ophthalmoscopy or neurobehavioural observations, and motor activity. Transient reductions in food intake and body weight gain in the mid-and high-dose group were ascribed to decreased palatability of the test feed. Only in males of the high-dose group the body weights remained slightly reduced throughout the study. In the high-dose group the number of thrombocytes (females), and total white blood cell count (males) were increased. Plasma triglycerides were dose-dependently depressed in males of all test groups and in females of the mid- and high-dose group, while plasma total cholesterol, and phospholipids were decreased in high-dose males. These changes, which have also been reported for other (flaxseed) lignans, were not considered to represent adverse effects. The relative weight of the kidneys was increased in males of the high-dose group. The weight of the full and empty caecum showed dose-related increases in males of all treatment groups and in females of the high-dose group. Absolute ovary weights were decreased in all treatment groups while decreases in relative ovary weights were confined to the mid- and high-dose group. In addition, a marginal lengthening of the estrus cycle was noted in high-dose females. Apart from prevention of hyaline droplet nephropathy in all high-dose male rats, there were no treatment-related histopathological alterations. It was concluded that HMRlignan showed weak antiestrogen-like activity which may be mediated through enterolactone metabolite. Based on declined ovary weight, the no observed adverse effect level of HMRlignan was set at 0.25% in feed corresponding to 160 mg/kg body

Topics: 4-Butyrolactone; Animals; Body Weight; Diet; Female; Lignans; Male; Motor Activity; No-Observed-Adverse-Effect Level; Organ Size; Potassium Acetate; Rats; Rats, Wistar