Nutrition & Metabolism | |
The flavonoid, naringenin, decreases adipose tissue mass and attenuates ovariectomy-associated metabolic disturbances in mice | |
Martha A Belury5  Lisa D Yee1  Shana R Straka1  Rebecca R Andridge3  Kimerly A Powell2  Rachel M Cole5  Essam M Hamad4  Kara L Kliewer5  Jia-Yu Ke5  | |
[1] Department of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio, USA;Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, Ohio, USA;Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, Ohio, USA;Department of Dairy Science, Faculty of Agriculture, Cairo University, Giza, Egypt;Department of Human Sciences, Human Nutrition Program, College of Education and Human Ecology, The Ohio State University, Campbell Hall 302, 1787 Neil Avenue, Columbus, Ohio 43210, USA | |
关键词: Fatty liver; Adipose tissue inflammation; Insulin sensitivity; Obesity; Menopause; Naringenin; | |
Others : 1130850 DOI : 10.1186/1743-7075-12-1 |
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received in 2014-09-22, accepted in 2014-12-23, 发布年份 2015 | |
【 摘 要 】
Objective
Adverse metabolic changes associated with loss of ovarian function increase the risk of developing metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) in postmenopausal women. Naringenin improves metabolic disturbances in vitro and in vivo. In the present study, we tested the effects of naringenin on metabolic disturbances resulting from estrogen deficiency in ovariectomized mice.
Materials/methods
Ovariectomized C57BL/6 J female mice were fed a control diet (10% calories from fat) for 11 weeks. Mice either continued on the control diet (n = 9) or were switched to the control diet supplemented with 3% naringenin (n = 10) for the next 11 weeks. Energy expenditure was measured by indirect calorimetry and activity was monitored by infrared beam breaks. Intra-abdominal and subcutaneous adiposity was evaluated by magnetic resonance imaging (MRI). Blood biochemical measures of metabolic response included glucose, insulin, adipokines, and lipids. Lipid content in liver and muscle and expression of relevant genes in adipose tissue, liver, and muscle were quantified.
Results
Ovariectomized mice fed naringenin exhibited lower fasting glucose and insulin levels compared to controls, with over 50% reduction of intra-abdominal and subcutaneous adiposity. Plasma leptin and leptin mRNA in adipose depots were also decreased in mice fed a naringenin diet. Monocyte chemoattractant protein-1 (MCP1/Ccl2) and interleukin 6 (IL-6/Il6) mRNA expression levels were significantly lower in perigonadal adipose tissue of naringenin-supplemented mice. We also observed that mice fed a naringenin diet had less hepatic lipid accumulation with corresponding alterations of hepatic gene expression associated with de novo lipogenesis, fatty acid oxidation, and gluconeogenesis.
Conclusion
Dietary naringenin attenuates many of the metabolic disturbances associated with ovariectomy in female mice.
【 授权许可】
2015 Ke et al.; licensee BioMed Central.
【 预 览 】
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【 参考文献 】
- [1]Davis SR, Castelo-Branco C, Chedraui P, Lumsden MA, Nappi RE, Shah D, et al.: Understanding weight gain at menopause. Climacteric 2012, 15:419-429.
- [2]Kaaja RJ: Metabolic syndrome and the menopause. Menopause Int 2008, 14:21-25.
- [3]Suzuki A, Abdelmalek MF: Nonalcoholic fatty liver disease in women. Womens Health (Lond Engl) 2009, 5:191-203.
- [4]Barrett-Connor E: Menopause, atherosclerosis, and coronary artery disease. Curr Opin Pharmacol 2013, 13:186-191.
- [5]Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al.: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002, 288:321-333.
- [6]Terao J: Dietary flavonoids as antioxidants. Forum Nutr 2009, 61:87-94.
- [7]Meydani M, Hasan ST: Dietary polyphenols and obesity. Nutrients 2010, 2:737-751.
- [8]Davies JN, Hobson GE: The constituents of tomato fruit–the influence of environment, nutrition, and genotype. Crit Rev Food Sci Nutr 1981, 15:205-280.
- [9]Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M: Quantitation of flavonoid constituents in citrus fruits. J Agric Food Chem 1999, 47:3565-3571.
- [10]Purushotham A, Tian M, Belury MA: The citrus fruit flavonoid naringenin suppresses hepatic glucose production from Fao hepatoma cells. Mol Nutr Food Res 2009, 53:300-307.
- [11]Huong DT, Takahashi Y, Ide T, et al.: Activity and mRNA levels of enzymes involved in hepatic fatty acid oxidation in mice fed citrus flavonoids. Nutrition 2006, 22:546-552.
- [12]Mulvihill EE, Allister EM, Sutherland BG, Telford DE, Sawyez CG, Edwards JY, et al.: Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and hyperinsulinemia in LDL receptor-null mice with diet-induced insulin resistance. Diabetes 2009, 58:2198-2210.
- [13]Cho KW, Kim YO, Andrade JE, Burgess JR, Kim YC: Dietary naringenin increases hepatic peroxisome proliferators-activated receptor alpha protein expression and decreases plasma triglyceride and adiposity in rats. Eur J Nutr 2011, 50:81-88.
- [14]Goldwasser J, Cohen PY, Yang E, Balaguer P, Yarmush ML, Nahmias Y: Transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin: role of PPARalpha. PPARgamma and LXRalpha. PLoS One 2010, 5:e12399.
- [15]Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD: Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Adv Nutr 2014, 5:404-417.
- [16]Rogers NH, Perfield JW 2nd, Strissel KJ, Obin MS, Greenberg AS, et al.: Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity. Endocrinology 2009, 150:2161-2168.
- [17]Vieira Potter VJ, Strissel KJ, Xie C, Chang E, Bennett G, Defuria J, et al.: Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity. Endocrinology 2012, 153:4266-4277.
- [18]Peters J: Animal and Human Calorimetry - Mclean, Ja, Tobin, C. American Journal of Physical Anthropology 1989, 78:127-127.
- [19]Folch J, Lees M, Sloane Stanley GH: A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957, 226:497-509.
- [20]Pacheco YM, Perez-Camino MC, Cert A, Montero E, Ruiz-Gutierrez V: Determination of the molecular species composition of diacylglycerols in human adipose tissue by solid-phase extraction and gas chromatography on a polar phase. J Chromatogr B Biomed Sci Appl 1998, 714:127-132.
- [21]Danno H, Jincho Y, Budiyanto S, Furukawa Y, Kimura S: A simple enzymatic quantitative analysis of triglycerides in tissues. J Nutr Sci Vitaminol (Tokyo) 1992, 38:517-521.
- [22]Wendel AA, Purushotham A, Liu LF, Belury MA: Conjugated linoleic acid fails to worsen insulin resistance but induces hepatic steatosis in the presence of leptin in ob/ob mice. J Lipid Res 2008, 49:98-106.
- [23]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001, 25:402-408.
- [24]Tschop MH, Speakman JR, Arch JR, Auwerx J, Bruning JC, Chan L, et al.: A guide to analysis of mouse energy metabolism. Nat Methods 2012, 9:57-63.
- [25]Ryan AS, Elahi D: The effects of acute hyperglycemia and hyperinsulinemia on plasma leptin levels: its relationships with body fat, visceral adiposity, and age in women. J Clin Endocrinol Metab 1996, 81:4433-4438.
- [26]Lavoie JM, Pighon A: NAFLD, Estrogens, and Physical Exercise: The Animal Model. J Nutr Metab 2012, 2012:914938.
- [27]Leite RD, Prestes J, Bernardes CF, Shiguemoto GE, Pereira GB, Duarte JO, et al.: Effects of ovariectomy and resistance training on lipid content in skeletal muscle, liver, and heart; fat depots; and lipid profile. Appl Physiol Nutr Metab 2009, 34:1079-1086.
- [28]Jou J, Choi SS, Diehl AM: Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis 2008, 28:370-379.
- [29]Kallwitz ER, McLachlan A, Cotler SJ: Role of peroxisome proliferators-activated receptors in the pathogenesis and treatment of nonalcoholic fatty liver disease. World J Gastroenterol 2008, 14:22-28.
- [30]Xue F, Michels KB: Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence. Am J Clin Nutr 2007, 86:s823-835.
- [31]Carr MC: The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab 2003, 88:2404-2411.
- [32]Assini JM, Mulvihill EE, Sutherland BG, Telford DE, Sawyez CG, Felder SL, et al.: Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr(-)/(-) mice. J Lipid Res 2013, 54:711-724.
- [33]Kannappan S, Anuradha CV: Naringenin enhances insulin-stimulated tyrosine phosphorylation and improves the cellular actions of insulin in a dietary model of metabolic syndrome. Eur J Nutr 2010, 49:101-109.
- [34]Mulvihill EE, Assini JM, Sutherland BG, DiMattia AS, Khami M, Koppes JB, et al.: Naringenin decreases progression of atherosclerosis by improving dyslipidemia in high-fat-fed low-density lipoprotein receptor-null mice. Arterioscler Thromb Vasc Biol 2010, 30:742-748.
- [35]Yoshida H, Watanabe W, Oomagari H, Tsuruta E, Shida M, Kurokawa M: Citrus flavonoid naringenin inhibits TLR2 expression in adipocytes. J Nutr Biochem 2013, 24:1276-1284.
- [36]Brown LM, Clegg DJ: Central effects of estradiol in the regulation of food intake, body weight, and adiposity. J Steroid Biochem Mol Biol 2010, 122:65-73.
- [37]Witte MM, Resuehr D, Chandler AR, Mehle AK, Overton JM: Female mice and rats exhibit species-specific metabolic and behavioral responses to ovariectomy. Gen Comp Endocrinol 2010, 166:520-528.
- [38]D'Eon TM, Souza SC, Aronovitz M, Obin MS, Fried SK, Greenberg AS: Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. J Biol Chem 2005, 280:35983-35991.
- [39]Ludgero-Correia A Jr, Aguila MB, Mandarim-de-Lacerda CA, Faria TS: Effects of high-fat diet on plasma lipids, adiposity, and inflammatory markers in ovariectomized C57BL/6 mice. Nutrition 2012, 28:316-323.
- [40]Lovejoy JC, Champagne CM, de Jonge L, Xie H, Smith SR: Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes (Lond) 2008, 32:949-958.
- [41]Sowers M, Zheng H, Tomey K, Karvonen-Gutierrez C, Jannausch M, Li X, et al.: Changes in body composition in women over six years at midlife: ovarian and chronological aging. J Clin Endocrinol Metab 2007, 92:895-901.
- [42]Hong J, Stubbins RE, Smith RR, Harvey AE, Nunez NP: Differential susceptibility to obesity between male, female and ovariectomized female mice. Nutr J 2009, 8:11. BioMed Central Full Text
- [43]Pfeilschifter J, Koditz R, Pfohl M, Schatz H: Changes in proinflammatory cytokine activity after menopause. Endocr Rev 2002, 23:90-119.
- [44]Lee CG, Carr MC, Murdoch SJ, Mitchell E, Woods NF, Wener MH, et al.: Adipokines, inflammation, and visceral adiposity across the menopausal transition: a prospective study. J Clin Endocrinol Metab 2009, 94:1104-1110.
- [45]Kim WK, Choi EK, Sul OJ, Park YK, Kim ES, Yu R, et al.: Monocyte chemoattractant protein-1 deficiency attenuates oxidative stress and protects against ovariectomy-induced chronic inflammation in mice. PLoS One 2013, 8:e72108.
- [46]Borradaile NM, de Dreu LE, Huff MW: Inhibition of net HepG2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation. Diabetes 2003, 52:2554-2561.
- [47]Paquette A, Shinoda M, Rabasa Lhoret R, Prud'homme D, Lavoie JM: Time course of liver lipid infiltration in ovariectomized rats: impact of a high-fat diet. Maturitas 2007, 58:182-190.
- [48]Paquette A, Wang D, Jankowski M, Gutkowska J, Lavoie JM: Effects of ovariectomy on PPAR alpha, SREBP-1c, and SCD-1 gene expression in the rat liver. Menopause 2008, 15:1169-1175.
- [49]Wohlers LM, Jackson KC, Spangenburg EE: Lipolytic signaling in response to acute exercise is altered in female mice following ovariectomy. J Cell Biochem 2011, 112:3675-3684.
- [50]Wohlers LM, Spangenburg EE: 17beta-estradiol supplementation attenuates ovariectomy-induced increases in ATGL signaling and reduced perilipin expression in visceral adipose tissue. J Cell Biochem 2010, 110:420-427.
- [51]Stubbins RE, Najjar K, Holcomb VB, Hong J, Nunez NP: Oestrogen alters adipocyte biology and protects female mice from adipocyte inflammation and insulin resistance. Diabetes Obes Metab 2012, 14:58-66.
- [52]Erlund I, Meririnne E, Alfthan G, Aro A: Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J Nutr 2001, 131:235-241.
- [53]Bugianesi R, Catasta G, Spigno P, D'Uva A, Maiani G: Naringenin from cooked tomato paste is bioavailable in men. J Nutr 2002, 132:3349-3352.