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Horm Metab Res 2010; 42(3): 187-193
DOI: 10.1055/s-0029-1242746
Animals, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Cinnamon Extract Regulates Plasma Levels of Adipose-derived Factors and Expression of Multiple Genes Related to Carbohydrate Metabolism and Lipogenesis in Adipose Tissue of Fructose-fed Rats

B. Qin1 , 2 , M. M. Polansky1 , R. A. Anderson1
  • 1Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U. S. Department of Agriculture, Beltsville, Maryland, USA
  • 2Integrity Nutraceuticals International, 3005 Parkfield Loop, South Spring Hill, TN, USA
Further Information

Publication History

received 21.08.2009

accepted 26.10.2009

Publication Date:
23 November 2009 (online)

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Abstract

We reported earlier that dietary cinnamon extract (CE) improves systemic insulin sensitivity and dyslipidemia by enhancing insulin signaling. In the present study, we have examined the effects of CE on several biomarkers including plasma levels of adipose-derived adipokines, and the potential molecular mechanisms of CE in epididymal adipose tissue (EAT). In Wistar rats fed a high-fructose diet (HFD) to induce insulin resistance, supplementation with a CE (Cinnulin PF®, 50 mg/kg daily) for 8 weeks reduced blood glucose, plasma insulin, triglycerides, total cholesterol, chylomicron-apoB48, VLDL-apoB100, and soluble CD36. CE also inhibited plasma retinol binding protein 4 (RBP4) and fatty acid binding protein 4 (FABP4) levels. CE-induced increases in plasma adiponectin were not significant. CE did not affect food intake, bodyweight, and EAT weight. In EAT, there were increases in the insulin receptor (Ir) and Ir substrate 2 (Irs2) mRNA, but CE-induced increases in mRNA expression of Irs1, phosphoinositide-3-kinase, Akt1, glucose transporters 1 and 4, and glycogen synthase 1 expression and decreased trends in mRNA expression of glycogen synthase kinase 3β were not statistically significant. CE also enhanced the mRNA levels of adipoQ, and inhibited sterol regulatory element binding protein-1c mRNA levels. mRNA and protein levels of fatty acid synthase and FABP4 were inhibited by CE and RBP4, and CD36 protein levels were also decreased by CE. These results suggest that CE effectively ameliorates circulating levels of adipokines partially mediated via regulation of the expression of multiple genes involved in insulin sensitivity and lipogenesis in the EAT.

Key words

cinnamon extract - adiponectin - FABP4 - RBP4 - adipose tissue

References

  • 1 Alberti KG, Zimmet P, Shaw J. Metabolic syndrome – a new world-wide definition. A Consensus Statement from the International Diabetes Federation.  Diabet Med. 2006;  23 469-480
    Google Scholar
  • 2 Ahima RS, Flier JS. Adipose tissue as an endocrine organ.  Trends Endocrinol Metab. 2000;  11 327-332
    Google Scholar
  • 3 Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.  Nat Med. 2001;  7 941-946
    Google Scholar
  • 4 Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.  J Clin Endocrinol Metab. 2001;  86 1930-1935
    Google Scholar
  • 5 Iacobellis G, di Gioia CR, Cotesta D, Petramala L, Travaglini C, De SV, Vitale D, Tritapepe L, Letizia C. Epicardial adipose tissue adiponectin expression is related to intracoronary adiponectin levels.  Horm Metab Res. 2009;  41 227-231
    Google Scholar
  • 6 Hunt CR, Ro JH, Dobson DE, Min HY, Spiegelman BM. Adipocyte P2 gene: developmental expression and homology of 5-flanking sequences among fat cell-specific genes.  Proc Natl Acad Sci USA. 1986;  83 3786-3790
    Google Scholar
  • 7 Boord JB, Maeda K, Makowski L, Babaev VR, Fazio S, Linton MF, Hotamisligil GS. Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice.  Circulation. 2004;  110 1492-1498
    Google Scholar
  • 8 Makowski L, Boord JB, Maeda K, Babaev VR, Uysal KT, Morgan MA, Parker RA, Suttles J, Fazio S, Hotamisligil GS, Linton MF. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis.  Nat Med. 2001;  7 699-705
    Google Scholar
  • 9 Yeung DC, Xu A, Cheung CW, Wat NM, Yau MH, Fong CH, Chau MT, Lam KS. Serum adipocyte fatty acid-binding protein levels were independently associated with carotid atherosclerosis.  Arterioscler Thromb Vasc Biol. 2007;  27 1796-1802
    Google Scholar
  • 10 Xu A, Wang Y, Xu JY, Stejskal D, Tam S, Zhang J, Wat NM, Wong WK, Lam KS. Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome.  Clin Chem. 2006;  52 405-413
    Google Scholar
  • 11 Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L, Kahn BB. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes.  Nature. 2005;  436 356-362
    Google Scholar
  • 12 Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, Wason CJ, Oberbach A, Jansson PA, Smith U, Kahn BB. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects.  N Engl J Med. 2006;  354 2552-2563
    Google Scholar
  • 13 Polonsky KS. Retinol-binding protein 4, insulin resistance, and type 2 diabetes.  N Engl J Med. 2006;  354 2596-2598
    Google Scholar
  • 14 Sirtori CR, Galli C, Anderson JW, Arnoldi A. Nutritional and nutraceutical approaches to dyslipidemia and atherosclerosis prevention: Focus on dietary proteins.  Atherosclerosis. 2009;  203 8-17
    Google Scholar
  • 15 Anderson RA, Broadhurst CL, Polansky MM, Schmidt WF, Khan A, Flanagan VP, Schoene NW, Graves DJ. Isolation and characterization of polyphenol type-A polymers from cinnamon with insulin-like biological activity.  J Agric Food Chem. 2004;  52 65-70
    Google Scholar
  • 16 Broadhurst CL, Polansky MM, Anderson RA. Insulin-like biological activity of culinary and medicinal plant aqueous extracts in vitro.  J Agric Food Chem. 2000;  48 849-852
    Google Scholar
  • 17 Imparl-Radosevich J, Deas S, Polansky MM, Baedke DA, Ingebritsen TS, Anderson RA, Graves DJ. Regulation of PTP-1 and insulin receptor kinase by fractions from cinnamon: implications for cinnamon regulation of insulin signalling.  Horm Res. 1998;  50 177-182
    Google Scholar
  • 18 Qin B, Nagasaki M, Ren M, Bajotto G, Oshida Y, Sato Y. Cinnamon extract (traditional herb) potentiates in vivo insulin-regulated glucose utilization via enhancing insulin signaling in rats.  Diabetes Res Clin Pract. 2003;  62 139-148
    Google Scholar
  • 19 Ziegenfuss TN, Hofheins JE, Mendel RW, Landis J, Anderson RA. Effects of a water-soluble cinnamon extract on body composition and features of the metabolic syndrome in pre-diabetic men and women.  J Int Soc Sports Nutr. 2006;  3 45-53
    Google Scholar
  • 20 Roussel AM, Hininger I, Benaraba R, Ziegenfuss TN, Anderson RA. Antioxidant effects of a cinnamon extract in people with impaired fasting glucose that are overweight or obese.  J Am Coll Nutr. 2009;  28 16-21
    Google Scholar
  • 21 Wang JG, Anderson RA, Graham GM, III, Chu MC, Sauer MV, Guarnaccia MM, Lobo RA. The effect of cinnamon extract on insulin resistance parameters in polycystic ovary syndrome: a pilot study.  Fertil Steril. 2007;  88 240-243
    Google Scholar
  • 22 Qin B, Polansky MM, Sato Y, Adeli K, Anderson RA. Cinnamon extract inhibits the postprandial overproduction of apolipoprotein B48-containing lipoproteins in fructose-fed animals.  J Nutr Biochem. 2009;  20 901-908
    Google Scholar
  • 23 Qin B, Dawson H, Polansky MM, Anderson RA. Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin, and lipoprotein pathways in enterocytes.  Horm Metab Res. 2009;  41 516-522
    Google Scholar
  • 24 Federico LM, Naples M, Taylor D, Adeli K. Intestinal insulin resistance and aberrant production of apolipoprotein B48 lipoproteins in an animal model of insulin resistance and metabolic dyslipidemia: evidence for activation of protein tyrosine phosphatase-1B, extracellular signal-related kinase, and sterol regulatory element-binding protein-1c in the fructose-fed hamster intestine.  Diabetes. 2006;  55 1316-1326
    Google Scholar
  • 25 Qin B, Qiu W, Avramoglu RK, Adeli K. Tumor necrosis factor-alpha induces intestinal insulin resistance and stimulates the overproduction of intestinal apolipoprotein B48-containing lipoproteins.  Diabetes. 2007;  56 450-461
    Google Scholar
  • 26 Qin B, Anderson RA, Adeli K. Tumor necrosis factor-alpha directly stimulates the overproduction of hepatic apolipoprotein B100-containing VLDL via impairment of hepatic insulin signaling.  Am J Physiol Gastrointest Liver Physiol. 2008;  294 G1120-G1129
    Google Scholar
  • 27 Qin B, Nagasaki M, Ren M, Bajotto G, Oshida Y, Sato Y. Cinnamon extract prevents the insulin resistance induced by a high-fructose diet.  Horm Metab Res. 2004;  36 119-125
    Google Scholar
  • 28 Taghibiglou C, Carpentier A, Van Iderstine SC, Chen B, Rudy D, Aiton A, Lewis GF, Adeli K. Mechanisms of hepatic very low density lipoprotein overproduction in insulin resistance. Evidence for enhanced lipoprotein assembly, reduced intracellular ApoB degradation, and increased microsomal triglyceride transfer protein in a fructose-fed hamster model.  J Biol Chem. 2000;  275 8416-8425
    Google Scholar
  • 29 Taghibiglou C, Rashid-Kolvear F, Van Iderstine SC, Le Tien H, Fantus IG, Lewis GF, Adeli K. Hepatic very low density lipoprotein-ApoB overproduction is associated with attenuated hepatic insulin signaling and overexpression of protein-tyrosine phosphatase 1B in a fructose-fed hamster model of insulin resistance.  J Biol Chem. 2002;  277 793-803
    Google Scholar
  • 30 Ukkola O, Santaniemi M. Adiponectin: a link between excess adiposity and associated comorbidities?.  J Mol Med. 2002;  80 696-702
    Google Scholar
  • 31 Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity.  J Biol Chem. 1996;  271 10697-10703
    Google Scholar
  • 32 Combs TP, Pajvani UB, Berg AH, Lin Y, Jelicks LA, Laplante M, Nawrocki AR, Rajala MW, Parlow AF, Cheeseboro L, Ding YY, Russell RG, Lindemann D, Hartley A, Baker GR, Obici S, Deshaies Y, Ludgate M, Rossetti L, Scherer PE. A transgenic mouse with a deletion in the collagenous domain of adiponectin displays elevated circulating adiponectin and improved insulin sensitivity.  Endocrinology. 2004;  145 367-383
    Google Scholar
  • 33 Roffey B, Atwal A, Kubow S. Cinnamon water extracts increase glucose uptake but inhibit adiponectin secretion in 3T3-L1 adipose cells.  Mol Nutr Food Res. 2006;  50 739-745
    Google Scholar
  • 34 Seale AP, de Jesus LA, Park MC, Kim YS. Vanadium and insulin increase adiponectin production in 3T3-L1 adipocytes.  Pharmacol Res. 2006;  54 30-38
    Google Scholar
  • 35 Kamari Y, Peleg E, Herman MO, Bursztyn M, Grossman E, Sharabi Y. The effect of chronic hyperinsulinemia on plasma adiponectin levels in Sprague-Dawley rats.  Horm Metab Res. 2009;  41 46-49
    Google Scholar
  • 36 Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes.  Biochem Biophys Res Commun. 2002;  290 1084-1089
    Google Scholar
  • 37 Kim JB, Spiegelman BM. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism.  Genes Dev. 1996;  10 1096-1107
    Google Scholar
  • 38 Yang Y, Zhou L, Gu Y, Zhang Y, Tang J, Li F, Shang W, Jiang B, Yue X, Chen M. Dietary chickpeas reverse visceral adiposity, dyslipidaemia and insulin resistance in rats induced by a chronic high-fat diet.  Br J Nutr. 2007;  98 720-726
    Google Scholar
  • 39 Lee MS, Kim CT, Kim Y. Green Tea (–)-Epigallocatechin-3-Gallate Reduces Body Weight with Regulation of Multiple Genes Expression in Adipose Tissue of Diet-Induced Obese Mice.  Ann Nutr Metab. 2009;  54 151-157
    Google Scholar
  • 40 Hiremagalur BK, Vadlamudi S, Johanning GL, Patel MS. Long-term effects of feeding high carbohydrate diet in pre-weaning period by gastrostomy: a new rat model for obesity.  Int J Obes Relat Metab Disord. 1993;  17 495-502
    Google Scholar
  • 41 Guichard C, Dugail I, Le L, X, Lavau M. Genetic regulation of fatty acid synthetase expression in adipose tissue: overtranscription of the gene in genetically obese rats.  J Lipid Res. 1992;  33 679-687
    Google Scholar
  • 42 Tso AW, Xu A, Sham PC, Wat NM, Wang Y, Fong CH, Cheung BM, Janus ED, Lam KS. Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes: a 10-year prospective study in a Chinese cohort.  Diabetes Care. 2007;  30 2667-2672
    Google Scholar
  • 43 Xu A, Tso AW, Cheung BM, Wang Y, Wat NM, Fong CH, Yeung DC, Janus ED, Sham PC, Lam KS. Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study.  Circulation. 2007;  115 1537-1543
    Google Scholar
  • 44 Furuhashi M, Tuncman G, Gorgun CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF, Sulsky R, Robl JA, Parker RA, Hotamisligil GS. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2.  Nature. 2007;  447 959-965
    Google Scholar
  • 45 Boord JB, Maeda K, Makowski L, Babaev VR, Fazio S, Linton MF, Hotamisligil GS. Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice.  Circulation. 2004;  110 1492-1498
    Google Scholar
  • 46 Makowski L, Boord JB, Maeda K, Babaev VR, Uysal KT, Morgan MA, Parker RA, Suttles J, Fazio S, Hotamisligil GS, Linton MF. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis.  Nat Med. 2001;  7 699-705
    Google Scholar
  • 47 Maeda K, Cao H, Kono K, Gorgun CZ, Furuhashi M, Uysal KT, Cao Q, Atsumi G, Malone H, Krishnan B, Minokoshi Y, Kahn BB, Parker RA, Hotamisligil GS. Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes.  Cell Metab. 2005;  1 107-119
    Google Scholar
  • 48 Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, Wason CJ, Oberbach A, Jansson PA, Smith U, Kahn BB. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects.  N Engl J Med. 2006;  354 2552-2563
    Google Scholar
  • 49 Polonsky KS. Retinol-binding protein 4, insulin resistance, and type 2 diabetes.  N Engl J Med. 2006;  354 2596-2598
    Google Scholar
  • 50 Handberg A, Levin K, Hojlund K, Beck-Nielsen H. Identification of the oxidized low-density lipoprotein scavenger receptor CD36 in plasma: a novel marker of insulin resistance.  Circulation. 2006;  114 1169-1176
    Google Scholar
  • 51 Koonen DP, Febbraio M, Bonnet S, Nagendran J, Young ME, Michelakis ED, Dyck JR. CD36 expression contributes to age-induced cardiomyopathy in mice.  Circulation. 2007;  116 2139-2147
    Google Scholar
  • 52 Fischer-Posovszky P, Wabitsch M, Hochberg Z. Endocrinology of adipose tissue - an update.  Horm Metab Res. 2007;  39 314-321
    Google Scholar

Correspondence

B. QinMD, PhD 

USDA-ARS-BHNRC-DGIL Building

307C Room 215

10300 Baltimore Ave

Beltsville

MD 20705

USA

Phone: +1/301/504 52 53 (ext. 272)

Fax: +1/301/504 90 62

Email: Bolin.Qin@ars.usda.gov

R. A. AndersonPhD 

USDA-ARS-BHNRC-DGIL Building

307C Room 222

10300 Baltimore ave

Beltsville

MD 20705

USA

Phone: +1/301/504 80 91

Fax: +1/301/504 90 62

Email: Richard.Anderson@ars.usda.gov

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