title: 2-heptyl-formononetin increases cholesterol and induces hepatic steatosis in mice.
abstract: Consumption of isoflavones may prevent adiposity, hepatic steatosis, and dyslipidaemia. However, studies in the area are few and primarily with genistein. This study investigated the effects of formononetin and its synthetic analogue, 2-heptyl-formononetin (C7F), on lipid and cholesterol metabolism in C57BL/6J mice. The mice were fed a cholesterol-enriched diet for five weeks to induce hypercholesterolemia and were then fed either the cholesterol-enriched diet or the cholesterol-enriched diet-supplemented formononetin or C7F for three weeks. Body weight and composition, glucose homeostasis, and plasma lipids were compared. In another experiment, mice were fed the above diets for five weeks, and hepatic triglyceride accumulation and gene expression and histology of adipose tissue and liver were examined. Supplementation with C7F increased plasma HDL-cholesterol thereby increasing the plasma level of total cholesterol. Supplementation with formononetin did not affect plasma cholesterol but increased plasma triglycerides levels. Supplementation with formononetin and C7F induced hepatic steatosis. However, formononetin decreased markers of inflammation and liver injury. The development of hepatic steatosis was associated with deregulated expression of hepatic genes involved in lipid and lipoprotein metabolism. In conclusion, supplementation with formononetin and C7F to a cholesterol-enriched diet adversely affected lipid and lipoprotein metabolism in C57BL/6J mice.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Andersen
authors.forename: Janne G
authors.initials: JG
authors.lastname: Schjoldager
authors.forename: Christian G
authors.initials: CG
authors.lastname: Tortzen
authors.forename: Andreas
authors.initials: A
authors.lastname: Vegge
authors.forename: Majbritt R
authors.initials: MR
authors.lastname: Hufeldt
authors.forename: Mette T
authors.initials: MT
authors.lastname: Skaanild
authors.forename: Finn K
authors.initials: FK
authors.lastname: Vogensen
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.forename: Axel K
authors.initials: AK
authors.lastname: Hansen
authors.forename: John
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D015502:Absorptiometry, Photon; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000494:pharmacology; D019587:Dietary Supplements; D005234:Fatty Liver / Q000097:blood* / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D005951:Glucose Tolerance Test; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D007529:Isoflavones / Q000009:adverse effects*; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008066:Lipolysis / Q000187:drug effects / Q000235:genetics; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
chemical_list: D002784:Cholesterol; D002791:Cholesterol, Dietary; D005982:Glutathione Transferase; D007529:Isoflavones; D008074:Lipoproteins; D020011:Protective Agents; D014280:Triglycerides; C584672:2-heptylformononetin; C007768:formononetin