title: Dietary nitrite reverses features of postmenopausal metabolic syndrome induced by high-fat diet and ovariectomy in mice.
abstract: Menopausal women are at greater risk of developing metabolic syndrome with reduced endothelial nitric oxide synthase (eNOS) activity. Hormone replacement therapy increases eNOS activity and normalizes some characteristics of metabolic syndrome. We hypothesized that nitric oxide (NO) supplementation should have a therapeutic effect on this syndrome. We examined the effect of dietary nitrite in a mouse model with postmenopausal metabolic syndrome induced by ovariectomy (OVX) and a high fat diet (HF). C57BL/6 female mice were divided into five groups, sham+normal fat diet (NF), sham+ HF, OVX+HF with or without sodium nitrite (50 mg and 150 mg/l) in the drinking water. Daily food intake and weekly body weight were monitored for 18 wk. OVX and HF significantly reduced plasma levels of nitrate/nitrite (NOx), and mice developed obesity with visceral hypertrophic adipocytes and increased transcriptional levels of monocyte chemoattractant protein-1, TNF-α, and IL-6 in visceral fat tissues. The proinflammatory state in the adipocytes provoked severe hepatosteatosis and insulin resistance in OVX+HF group compared with sham+NF group. However, dietary nitrite significantly suppressed adipocyte hypertrophy and transcriptions of proinflammatory cytokines in visceral fat in a dose-dependent manner. The improvement of visceral inflammatory state consequently reversed the hepatosteatosis and insulin resistance observed in OVX+HF mice. These results suggest that an endogenous NO defect might underlie postmenopausal metabolic syndrome and that dietary nitrite provides an alternative source of NO, subsequently compensating for metabolic impairments of this syndrome.
authors.affiliation: Division of Pathophysiology, Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Science, Josai University, Saitama, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohtake
authors.affiliation: Division of Pathophysiology, Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Science, Josai University, Saitama, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ehara
authors.affiliation: Laboratory of Applied Nutrition, Division of Pathophysiology Department of Nutrition and Life Science, Kanagawa Institute of Technology, Kanagawa, Japan.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Chiba
authors.affiliation: Division of Pathophysiology, Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Science, Josai University, Saitama, Japan.
authors.forename: Genya
authors.initials: G
authors.lastname: Nakano
authors.affiliation: Department of Food and Nutritional Environment, College of Human Life and Environment, Kinjo Gakuin University, Nagoya, Japan; and.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Sonoda
authors.affiliation: Division of Oral Anatomy, Department of Human Development and Fostering, Meikai University School of Dentistry, Saitama, Japan.
authors.forename: Junta
authors.initials: J
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
authors.affiliation: Division of Pathophysiology, Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Science, Josai University, Saitama, Japan; junkoba@josai.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D004032:Diet; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects; D005234:Fatty Liver / Q000378:metabolism; D005260:Female; D007333:Insulin Resistance / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D009573:Nitrites / Q000008:administration & dosage / Q000627:therapeutic use*; D010052:Ovariectomy; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha
keywords: metabolic syndrome; nitric oxide; nitrite; ovariectomy; postmenopause