Abstract
Purpose
A metabolic abnormality such as obesity is a major obstacle in the maintenance of the human health system and causes various chronic diseases including type 2 diabetes, hypertension, cardiovascular diseases, as well as various cancers. This study was designed to summarize the recent scientific knowledge regarding the anti-obesity role of curcumin (diferuloylmethane), which is isolated from the herb curcuma longa, known to possess anti-inflammatory activities. However, little is known about its exact underlying molecular mechanisms in the treatment of obesity and metabolic diseases. Furthermore, cell cultures, animal models of obesity, and few human clinical and epidemiological studies have added the promise for future therapeutic interventions of this dietary compound.
Methods
An electronic search was performed using Science finder, Medline, Scopus, Google scholar and collected English language articles from 2000 to 2010, relating to the role of curcumin in obesity and metabolic diseases.
Results
Obesity has been classified as a growing epidemic and its associated metabolic disorders are considered a major risk to the health system. Curcumin interacts with specific proteins in adipocytes, pancreatic cells, hepatic stellate cells, macrophages, and muscle cells, where it suppresses several cellular proteins such as transcription factor NF-kB, STAT-3, Wnt/β-catenin and activates PPAR-γ, Nrf2 cell signaling pathway. In addition, curcumin downregulates the inflammatory cytokines, resistin and leptin, and upregulates adiponectin as well as other associated proteins. The interactions of curcumin with several signal transduction pathways reverse insulin resistance, hyperglycemia, hyperlipidemia, and other inflammatory symptoms associated with obesity and metabolic diseases.
Conclusion
The modulation of several cellular transduction pathways by curcumin has recently been extended to elucidate the molecular basis for obesity and obesity-related metabolic diseases. These findings might enable novel phytochemical treatment strategies as well as curcumin translation to the clinical practice for the treatment and prevention of obesity-related chronic diseases. Furthermore, the relatively low cost of curcumin, safety and proven efficacy make it advisable to include curcumin as part of healthy diet.
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References
DC C (2005) State-specific prevalence of obesity among adults—United States. MMWR 55:985–988
Health Survey for England (2007) http://www.ic.nhs.uk/statistics-and-datacollections/health-and-lifestyles-related-surveys/health-survey-forengland/health-survey for england-2007-latest-trends-%5Bns%5D
Flier JS (2004) Obesity wars: molecular progress confronts an expanding epidemic. Cell 116(2):337–350
Spiegelman BM, Flier JS (2001)Obesity and the regulation of energy balance. Cell 104(4):531–543
Friedman JM (2000) Obesity in the new millennium. Nature 404(6778):632–634
Barsh GS, Farooqi IS, O’Rahilly S (2000) Genetics of body-weight regulation. Nature 404(6778):644–651
Luchsinger JA (2006) A work in progress: the metabolic syndrome. Sci Aging Knowl Environ (10):pe19
Anand P, Kunnumakkara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B, Aggarwal BB (2008) Cancer is a preventable disease that requires major lifestyle changes. Pharm Res 25(9):2097–2116
IARC handbooks of cancer prevention (2002) Weight control and physical activity, international agency for research on cancer, Lyon. France 6:1–315
Shehzad A, Lee YS (2010) Curcumin: multiple molecular targets mediate multiple pharmacological actions. Drugs Future 35(2):113–119
Shehzad A, Wahid F, Lee YS (2010) Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch Pharm Chem Life Sci 343(9):489–499
Schenk S, Saberi M, Olefsky JM (2008) Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest 118(9):2992–3002
Roberts DL, Dive C, Renehan AG (2010) Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med 61:301–316
Wang P, Mariman E, Renes J, Keijer J (2008) The secretory function of adipocytes in the physiology of white adipose tissue. J Cell Physiol 216(1):3–13
Scherer PE (2006) Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes 55(6):1537–1545
Halberg N, Wernstedt-Asterholm I, Scherer PE (2008) The adipocyte as an endocrine cell. Endocrinol Metab Clin N Am 37(3):753–768
Hajri T, Tao H, Wattacheril J, Marks-Shulman P, Abumrad NN (2010) Regulation of adiponectin production by insulin: Interactions with tumor necrosis factor-alpha and interleukin-6. Am J Physiol Endocrinol Metab, doi:10.1152/ajpendo.00307
Moschen AR, Molnar C, Geiger S, Graziadei I, Ebenbichler CF, Weiss H, Kaser S, Kaser A, Tilg H (2010) Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor alpha expression. Gut 59(9):1259–1264
Lofgren P, Van H, Reynisdottir VS, Naslund E, Ryden M, Rossner S, Arner P (2000) Secretion of tumor necrosis factor-a shows a strong relationship to insulin-stimulated glucose transport in human adipose tissue. Diabetes 49(5):688–692
Zhang J, Gao Z, Yin J, Quon MJ, Ye J (2008) S6 K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2. J Biol Chem 283(51):35375–35382
Emanuelli B, Eberle D, Suzuki R, Kahn CR (2008) Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance. Proc Natl Acad Sci USA 105(9):3545–3550
Nieto-Vazquez I, Fernandez-Veledo S, Kramer DK, Vila-Bedmar R, Garcia-Guerra L, Lorenzo M (2008) Insulin resistance associated to obesity: the link TNF-alpha. Arch Physiol Biochem 114(3):183–194
Liang H, Yin B, Zhang H, Zhang S, Zeng Q, Wang J, Jiang X, Yuan L, Wang CY, Li Z (2008) Blockade of tumor necrosis factor (TNF) receptor type 1-mediated TNF-alpha signaling protected Wistar rats from diet-induced obesity and insulin resistance. Endocrinology 149(6):2943–2951
Tarantino G, Savastano S, Colao A (2010) Hepatic steatosis, low-grade chronic inflammation and hormone/growth factor/adipokine imbalance. World J Gastroenterol 16(38):4773–4783
Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE (2005) Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat Med 11(2):183–190
Shoelson SE, Lee J, Yuan M (2003) Inflammation and the IKKβ/Iκβ/NF-κB axis in obesity- and diet-induced insulin resistance. Int J Obes Relat Metab Disord (Suppl 3):S49–S52
Ahn KS, Sethi G, Aggarwal BB (2008) Reversal of chemoresistance and enhancement of apoptosis by statins through down-regulation of the NF-kappaB pathway. Biochem Pharmacol 75(4):907–913
Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116(11):3015–3025
Reyna SM, Ghosh S, Tantiwong P, Meka CS, Eagan P, Jenkinson CP, Cersosimo E, Defronzo RA, Coletta DK, Sriwijitkamol A, Musi N (2008) Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. Diabetes 57(10):2595–2602
Bennett BL, Satoh Y, Lewis AJ (2003) JNK: a new therapeutic target for diabetes. Curr Opin Pharmacol 3(4):420–425
Ogawa S, Lozach J, Jepsen K, Sawka-Verhelle D, Perissi V, Sasik R, Rose DW, Johnson RS, Rosenfeld MG, Glass CK (2004) A nuclear receptor corepressor transcriptional checkpoint controlling activator protein 1-dependent gene networks required for macrophage activation. Proc Natl Acad Sci USA 101(40):14461–14466
Huang W, Ghisletti S, Perissi V, Rosenfeld MG, Glass CK (2009) Transcriptional integration of TLR2 and TLR4 signaling at the NCoR depression checkpoint. Mol Cell 35(1):48–57
Moller DE (2001) New drug targets for type 2 diabetes and the metabolic syndrome. Nature 414(6865):821–827
Suzawa M, Takada I, Yanagisawa J, Ohtake F, Ogawa S, Yamauchi T, Kadowaki T, Takeuchi Y, Shibuya H, Gotoh Y, Matsumoto K, Kato S (2003) Cytokines suppress adipogenesis and PPAR-gamma function through the TAK1/TAB 1/NIK cascade. Nat Cell Biol 5(3):224–230
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112(12):1821–1830
Graham A (2009) Curcumin adds spice to the debate: lipid metabolism in liver disease. Br J Pharmacol 157(8):1352–1353
Shehzad A, Khan S, Shehzad O, Lee YS (2010) Curcumin therapeutic promises and bioavailability in colorectal cancer. Drugs Today 46(7):523–532
Yoysungnoen P, Wirachwong P, Bhattarakosol P, Niimi H, Patumraj S (2006) Effects of curcumin on tumor angiogenesis and biomarkers, COX-2 and VEGF, in hepatocellular carcinoma cell-implanted nude mice. Clin Hemorheol Microcirc 34(1–2):109–115
Woo HM, Kang JH, Kawada T, Yoo H, Sung MK, Yu R (2007) Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes. Life Sci 80(10):926–931
Jaiswal AS, Marlow BP, Gupta N, Narayan S (2002) Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene 21(55):8414–8427
Ahn J, Lee H, Kim S, Ha T (2010) Curcumin-induced suppression of adipogenic differentiation is accompanied by activation of Wnt/beta-catenin signaling. Am J Physiol Cell Physiol 298(6):C1510–C1516
Okada K, Wangpoengtrakul C, Tanaka T, Toyokuni S, Uchida K, Osawa T (2001) Curcumin and especially tetrahydrocurcumin ameliorate oxidative stress-induced renal injury in mice. J Nutr 131(8):2090–2095
Jain SK, Rains J, Jones K (2006) Effect of curcumin on protein glycosylation, lipid peroxidation, and oxygen radical generation in human red blood cells exposed to high glucose levels. Free Radic Biol Med 41(1):92–96
Peschel D, Koerting R, Nass N (2007) Curcumin induces changes in expression of genes involved in cholesterol homeostasis. J Nutr Biochem 18(2):113–119
Balogun E, Hoque M, Gong P, Killeen E, Green CJ, Foresti R, Alam J, Motterlini R (2003) Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J 371(Pt 3):887–895
Pendurthi UR, Rao LV (2000) Suppression of transcription factor Egr-1 by curcumin. Thromb Res 97(4):179–189
Tang Y, Zheng S, Chen A (2009) Curcumin eliminates leptin’s effects on hepatic stellate cell activation via interrupting leptin signaling. Endocrinology 150(7):3011–3020
Weisberg SP, Leibel R, Tortoriello DV (2009) Dietary curcumin significantly improves obesity-associated inflammation and diabetes in mouse models of diabesity. Endocrinology 149(7):3549–3558
Ejaz A, Wu D, Kwan P, Meydani M (2009) Curcumin inhibits adipogenesis in 3T3–L1 adipocytes and angiogenesis and obesity in C57/BL mice. J Nutr 139(5):919–925
Lee YK, Lee WS, Hwang JT, Kwon DY, Surh YJ, Park OJ (2009) Curcumin exerts antidifferentiation effect through AMPKalpha-PPAR-gamma in 3T3–L1 adipocytes and antiproliferatory effect through AMPKalpha-COX-2 in cancer cells. J Agric Food Chem 57(1):305–310
Wang SL, Li Y, Wen Y, Chen YF, Na LX, Li ST, Sun CH (2009) Curcumin, a potential inhibitor of up-regulation of TNF-alpha and IL-6 induced by palmitate in 3T3-L1 adipocytes through NF-kappaB and JNK pathway. Biomed Environ Sci 22(1):32–39
Lim JH, Kwon TK (2010) Curcumin inhibits phorbol myristate acetate (PMA)-induced MCP-1 expression by inhibiting ERK and NF-kappaB transcriptional activity. Food Chem Toxicol 48(1):47–52
Kang Q, Chen A (2009) Curcumin inhibits srebp-2 expression in activated hepatic stellate cells in vitro by reducing the activity of specificity protein-1. Endocrinology 150(12):5384–5394
Zheng S, Chen A (2006) Curcumin suppresses the expression of extracellular matrix genes in activated hepatic stellate cells by inhibiting gene expression of connective tissue growth factor. Am J Physiol Gastrointest Liver Physiol 290(5):G883–G893
Tang Y, Chen A (2010) Curcumin protects hepatic stellate cells against leptin-induced activation in vitro by accumulating intracellular lipids. Endocrinology 151(9):4168–4177
Tang Y, Chen A (2010) Curcumin prevents leptin raising glucose levels in hepatic stellate cells by blocking translocation of glucose transporter-4 and increasing glucokinase. Br J Pharmacol 161(5):1137–1149
Masamune A, Suzuki N, Kikuta K, Satoh M, Satoh K, Shimosegawa T (2006) Curcumin blocks activation of pancreatic stellate cells. J Cell Biochem 97(5):1080–1093
Balamurugan AN, Akhov L, Selvaraj G, Pugazhenthi S (2009) Induction of antioxidant enzymes by curcumin and its analogues in human islets: implications in transplantation. Pancreas 38(4):454–460
Kanitkar M, Gokhale K, Galande S, Bhonde RR (2008) Novel role of curcumin in the prevention of cytokine-induced islet death in vitro and diabetogenesis in vivo. Br J Pharmacol 155(5):702–713
Karthikesan K, Pari L, Menon VP (2010) Combined treatment of tetrahydrocurcumin and chlorogenic acid exerts potential antihyperglycemic effect on streptozotocin-nicotinamide-induced diabetic rats. Gen Physiol Biophys 29(1):23–30
Pongchaidecha A, Lailerd N, Boonprasert W, Chattipakorn N (2009) Effects of curcuminoid supplement on cardiac autonomic status in high-fat-induced obese rats. Nutrition 25(7–8):870–878
Morimoto T, Sunagawa Y, Kawamura T, Takaya T, Wada H, Nagasawa A, Komeda M, Fujita M, Shimatsu A, Kita T, Hasegawa K (2008) The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats. J Clin Invest 118(3):868–878
Quiles JL, Mesa MD, Ramirez-Tortosa CL, Aguilera CM, Battino M, Gil A, Ramírez-Tortosa MC (2002) Curcuma longa extract supplementation reduces oxidative stress and attenuates aortic fatty streak development in rabbits. Arterioscler Thromb Vasc Biol 22(7):1225–1231
Kutner NG, Johansen KL, Kaysen GA, Pederson S, Chen SC, Agodoa LY, Eggers PW, Chertow GM (2009) The Comprehensive Dialysis Study (CDS): A USRDS Special Study. Clin J Am Soc Nephrol 4:645–650
Chiu J, Khan ZA, Farhangkhoee H, Chakrabarti S (2009) Curcumin prevents diabetes-associated abnormalities in the kidneys by inhibiting p300 and nuclear factor-kappaB. Nutrition 25(9):964–972
Arun N, Nalini N (2002) Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats. Plant Foods Hum Nutr 57(1):41–52
Seo KI, Choi MS, Jung UJ, Kim HJ, Yeo J, Jeon SM, Lee MK (2008) Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Mol Nutr Food Res 52(9):995–1004
Kuhad A, Chopra K (2007) Curcumin attenuates diabetic encephalopathy in rats: behavioral and biochemical evidences. Eur J Pharmacol 576(1–3):34–42
Ramírez-Boscá A, Soler A, Carrión MA, Díaz-Alperi J, Bernd A, Quintanilla C, Quintanilla Almagro E, Miquel J (2000) An hydroalcoholic extract of Curcuma longa lowers the apo B/apo A ratio. Implications for atherogenesis prevention. Mech Ageing Dev 119(1–2):41–47
Ramirez Boscá A, Soler A, Carrión-Gutiérrez MA, Pamies Mira D, Pardo Zapata J, Diaz-Alperi J, Bernd A, Quintanilla Almagro E, Miquel J (2000) An hydroalcoholic extract of Curcuma longa lowers the abnormally high values of human-plasma fibrinogen. Mech Ageing Dev 114(3):207–210
Alwi I, Santoso T, Suyono S, Sutrisna B, Suyatna FD, Kresno SB, Ernie S (2008) The effect of curcumin on lipid level in patients with acute coronary syndrome. Acta Med Indones 40(4):201–210
Baum L, Cheung SK, Mok VC, Lam LC, Leung VP et al (2007) Curcumin effects on blood lipid profile in a 6-month human study. Pharmacol Res 56(6):509–514
Usharani P, Mateen AA, Naidu MU, Raju YS, Chandra N (2008) Effect of NCB-02, atorvastatin and placebo on endothelial function, oxidative stress and inflammatory markers in patients with type 2 diabetes mellitus: a randomized, parallel-group, placebo-controlled, 8-week study. Drugs R D 9(4):243–250
Chen Y, Liu WH, Chen BL, Fan L, Han Y, Wang G, Hu DL, Tan ZR, Zhou G, Cao S, Zhou HH (2010) Plant polyphenol curcumin significantly affects CYP1A2 and CYP2A6 activity in healthy, male Chinese volunteers. Ann Pharmacother 44(6):1038–1045
Belcaro G, Cesarone MR, Dugall M, Pellegrini L, Ledda A, Grossi MG, Togni S, Appendino G (2010) Product-evaluation registry of Meriva®, a curcumin-phosphatidylcholine complex, for the complementary management of osteoarthritis. Panminerva Med 52(2 Suppl 1):55–62
Allegri P, Mastromarino A, Neri P (2010) Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long-term follow-up. Clin Ophthalmol 4:1201–1206
Epelbaum R, Schaffer M, Vizel B, Badmaev V, Bar-Sela G (2010) Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer 62(8):1137–1141
Evaluation of Certain Food Additives (2000) WHO technical report series. WHO, Geneva, p 891
Liddle M, Hull C, Liu C, Powell D (2006) Contact urticaria from curcumin. Dermatitis 17(4):196–197
Rasyid A, Rahman AR, Jaalam K, Lelo A (2002) Effect of different curcumin dosages on human gall bladder. Asia Pac J Clin Nutr 11(4):314–318
Acknowledgments
This work was supported by Nuclear Research and Development Program of National Research Foundation of Korea funded by Ministry of Education, Science and Technology (grant code: 2010-0017517).
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Shehzad, A., Ha, T., Subhan, F. et al. New mechanisms and the anti-inflammatory role of curcumin in obesity and obesity-related metabolic diseases. Eur J Nutr 50, 151–161 (2011). https://doi.org/10.1007/s00394-011-0188-1
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DOI: https://doi.org/10.1007/s00394-011-0188-1
Keywords
- Curcumin
- Obesity
- Inflammation
- Adipocytes
- Adiponectin