Dietary Curcumin Significantly Improves Obesity-Associated Inflammation and Diabetes in Mouse Models of Diabesity

Endocrinology - Tập 149 Số 7 - Trang 3549-3558 - 2008
Stuart P. Weisberg1, Rudolph L. Leibel1, Drew V. Tortoriello1,2
1Diabetes and Endocrinology Research Center (S.P.W., R.L., D.V.T.), Columbia University, New York, New York 10032
2Sher Institute for Reproductive Medicine (D.V.T.), New York, New York 10016

Tóm tắt

Obesity is a major risk factor for the development of type 2 diabetes, and both conditions are now recognized to possess significant inflammatory components underlying their pathophysiologies. We tested the hypothesis that the plant polyphenolic compound curcumin, which is known to exert potent antiinflammatory and antioxidant effects, would ameliorate diabetes and inflammation in murine models of insulin-resistant obesity. We found that dietary curcumin admixture ameliorated diabetes in high-fat diet-induced obese and leptin-deficient ob/ob male C57BL/6J mice as determined by glucose and insulin tolerance testing and hemoglobin A1c percentages. Curcumin treatment also significantly reduced macrophage infiltration of white adipose tissue, increased adipose tissue adiponectin production, and decreased hepatic nuclear factor-κB activity, hepatomegaly, and markers of hepatic inflammation. We therefore conclude that orally ingested curcumin reverses many of the inflammatory and metabolic derangements associated with obesity and improves glycemic control in mouse models of type 2 diabetes. This or related compounds warrant further investigation as novel adjunctive therapies for type 2 diabetes in man.

Từ khóa


Tài liệu tham khảo

Calle, 2003, Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults., N Engl J Med, 348, 1625, 10.1056/NEJMoa021423

Kannel, 1991, Regional obesity and risk of cardiovascular disease: the Framingham Study., J Clin Epidemiol, 44, 183, 10.1016/0895-4356(91)90265-B

Kenchaiah, 2002, Obesity and the risk of heart failure., N Engl J Med, 347, 305, 10.1056/NEJMoa020245

Field, 2001, Impact of overweight on the risk of developing common chronic diseases during a 10-year period., Arch Intern Med, 161, 1581, 10.1001/archinte.161.13.1581

Must, 1999, The disease burden associated with overweight and obesity., JAMA, 282, 1523, 10.1001/jama.282.16.1523

Tortoriello, 2004, Dietary-induced obesity and hypothalamic infertility in female DBA/2J mice., Endocrinology, 145, 1238, 10.1210/en.2003-1406

Tortoriello, 2007, Increased expression of hypothalamic leptin receptor and adiponectin accompany resistance to dietary-induced obesity and infertility in female C57BL/6J mice., Int J Obes, 31, 395, 10.1038/sj.ijo.0803392

Metwally, 2007, The impact of obesity on female reproductive function., Obes Rev, 8, 515, 10.1111/j.1467-789X.2007.00406.x

Guelinckx, 2008, Maternal obesity: pregnancy complications, gestational weight gain and nutrition., Obes Rev, 9, 140, 10.1111/j.1467-789X.2007.00464.x

Daviglus, 2003, Body mass index in middle age and health-related quality of life in older age: the Chicago heart association detection project in industry study., Arch Intern Med, 163, 2448, 10.1001/archinte.163.20.2448

Hassan, 2003, Obesity and health-related quality of life: a cross-sectional analysis of the US population., Int J Obes Relat Metab Disord, 27, 1227, 10.1038/sj.ijo.0802396

Arterburn, 2005, Impact of morbid obesity on medical expenditures in adults., Int J Obes Relat Metab Disord, 29, 334, 10.1038/sj.ijo.0802896

Cinti, 2005, Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans., J Lipid Res, 46, 2347, 10.1194/jlr.M500294-JLR200

Weisberg, 2003, Obesity is associated with macrophage accumulation in adipose tissue., J Clin Invest, 112, 1796, 10.1172/JCI200319246

Rausch, 2007, Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration., Int J Obes, 32, 451, 10.1038/sj.ijo.0803744

Hotamisligil, 1993, Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance., Science, 259, 87, 10.1126/science.7678183

Uysal, 1997, Protection from obesity-induced insulin resistance in mice lacking TNF-α function., Nature, 389, 610, 10.1038/39335

Misonou, 2006, Acrolein produces nitric oxide through the elevation of intracellular calcium levels to induce apoptosis in human umbilical vein endothelial cells: implications for smoke angiopathy., Nitric Oxide, 14, 180, 10.1016/j.niox.2005.09.004

Suganami, 2007, Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation., Biochem Biophys Res Commun, 354, 45, 10.1016/j.bbrc.2006.12.190

Suganami, 2007, Role of the Toll-like receptor 4/NF-κB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages., Arterioscler Thromb Vasc Biol, 27, 84, 10.1161/01.ATV.0000251608.09329.9a

Tsukumo, 2007, Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance., Diabetes, 56, 1986, 10.2337/db06-1595

Poggi, 2007, C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet., Diabetologia, 50, 1267, 10.1007/s00125-007-0654-8

Arkan, 2005, IKK-β links inflammation to obesity-induced insulin resistance., Nat Med, 11, 191, 10.1038/nm1185

Yuan, 2001, Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ., Science, 293, 1673, 10.1126/science.1061620

Arafa, 2005, Curcumin attenuates diet-induced hypercholesterolemia in rats, Med Sci Monit, 11, BR228

Sharma, 2005, Curcumin: the story so far., Eur J Cancer, 41, 1955, 10.1016/j.ejca.2005.05.009

Shishodia, 2005, Curcumin: getting back to the roots., Ann NY Acad Sci, 1056, 206, 10.1196/annals.1352.010

Lao, 2006, Dose escalation of a curcuminoid formulation., BMC Complement Altern Med, 6, 10, 10.1186/1472-6882-6-10

Kunnumakkara, 2007, Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-κB-regulated gene products., Cancer Res, 67, 3853, 10.1158/0008-5472.CAN-06-4257

Shakibaei, 2007, Suppression of NF-κB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: implications for the treatment of osteoarthritis., Biochem Pharmacol, 73, 1434, 10.1016/j.bcp.2007.01.005

Gradisar, 2007, MD-2 as the target of curcumin in the inhibition of response to LPS., J Leukoc Biol, 82, 968, 10.1189/jlb.1206727

Bharti, 2004, Curcumin (diferuloylmethane) inhibits receptor activator of NF-κB ligand-induced NF-κB activation in osteoclast precursors and suppresses osteoclastogenesis., J Immunol, 172, 5940, 10.4049/jimmunol.172.10.5940

Srinivasan, 1972, Effect of curcumin on blood sugar as seen in a diabetic subject., Indian J Med Sci, 26, 269

Suresh Babu, 1998, Amelioration of renal lesions associated with diabetes by dietary curcumin in streptozotocin diabetic rats., Mol Cell Biochem, 181, 87, 10.1023/A:1006821828706

Sajithlal, 1998, Effect of curcumin on the advanced glycation and cross-linking of collagen in diabetic rats., Biochem Pharmacol, 56, 1607, 10.1016/S0006-2952(98)00237-8

Sidhu, 1999, Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice., Wound Repair Regen, 7, 362, 10.1046/j.1524-475X.1999.00362.x

Srivivasan, 2003, Protection of pancreatic β-cell by the potential antioxidant bis-o-hydroxycinnamoyl methane, analogue of natural curcuminoid in experimental diabetes., J Pharm Pharm Sci, 6, 327

Suryanarayana, 2005, Curcumin and turmeric delay streptozotocin-induced diabetic cataract in rats., Invest Ophthalmol Vis Sci, 46, 2092, 10.1167/iovs.04-1304

Kumar, 2005, Modulation of α-crystallin chaperone activity in diabetic rat lens by curcumin., Mol Vis, 11, 561

Mahesh, 2005, Effect of photo-irradiated curcumin treatment against oxidative stress in streptozotocin-induced diabetic rats., J Med Food, 8, 251, 10.1089/jmf.2005.8.251

Sharma, 2006, Curcumin attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic pain., Eur J Pharmacol, 536, 256, 10.1016/j.ejphar.2006.03.006

Woo, 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, 926, 10.1016/j.lfs.2006.11.030

Leibel, 1997, The molecular genetics of rodent single gene obesities., J Biol Chem, 272, 31937, 10.1074/jbc.272.51.31937

Bock, 2003, Increased islet volume but unchanged islet number in ob/ob mice., Diabetes, 52, 1716, 10.2337/diabetes.52.7.1716

Subauste, 2007, Role of FoxO1 in FFA-induced oxidative stress in adipocytes, Am J Physiol Endocrinol Metab, 293, E159, 10.1152/ajpendo.00629.2006

Qiao, 2006, SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein α transcriptional complex., J Biol Chem, 281, 39915, 10.1074/jbc.M607215200

Petersen, 2002, Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy., J Clin Invest, 109, 1345, 10.1172/JCI0215001

Javor, 2005, Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy., Hepatology, 41, 753, 10.1002/hep.20672

Thaloor, 1999, Systemic administration of the NF-κB inhibitor curcumin stimulates muscle regeneration after traumatic injury, Am J Physiol, 277, C320, 10.1152/ajpcell.1999.277.2.C320

Baghdiguian, 2001, Pathophysiology of limb girdle muscular dystrophy type 2A: hypothesis and new insights into the IκBα/NF-κB survival pathway in skeletal muscle., J Mol Med, 79, 254, 10.1007/s001090100225

Yamauchi, 2001, The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity., Nat Med, 7, 941, 10.1038/90984

Ahima, 2008, Adipokines in obesity., Front Horm Res, 36, 182, 10.1159/000115365

Guzik, 2006, Adipocytokines—novel link between inflammation and vascular function?, J Physiol Pharmacol, 57, 505

Qiang, 2007, Adiponectin secretion is regulated by SIRT1 and the endoplasmic reticulum oxidoreductase Ero1-Lα., Mol Cell Biol, 27, 4698, 10.1128/MCB.02279-06

Hanai, 2006, Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial., Clin Gastroenterol Hepatol, 4, 1502, 10.1016/j.cgh.2006.08.008

Sharma, 2004, Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance., Clin Cancer Res, 10, 6847, 10.1158/1078-0432.CCR-04-0744

Shoba, 1998, Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers., Planta Med, 64, 353, 10.1055/s-2006-957450