European Journal of Nutrition

, Volume 53, Issue 1, pp 149–158 | Cite as

Dietary cocoa ameliorates obesity-related inflammation in high fat-fed mice

  • Yeyi Gu
  • Shan Yu
  • Joshua D. LambertEmail author
Original Contribution



To investigate the effect of cocoa powder supplementation on obesity-related inflammation in high fat (HF)-fed obese mice.


Male C57BL/6J (n = 126) were fed with either low-fat (LF, 10 % kcal from fat) or HF (60 % kcal from fat) diet for 18 weeks. After 8 weeks, mice from HF group were randomized to HF diet or HF diet supplemented with 8 % cocoa powder (HF–HFC group) for 10 weeks. Blood and tissue samples were collected for biochemical analyses.


Cocoa powder supplementation significantly reduced the rate of body weight gain (15.8 %) and increased fecal lipid content (55.2 %) compared to HF-fed control mice. Further, cocoa supplementation attenuated insulin resistance, as indicated by improved HOMA-IR, and reduced the severity of obesity-related fatty liver disease (decreased plasma alanine aminotransferase and liver triglyceride) compared to HF group. Cocoa supplementation also significantly decreased plasma levels of the pro-inflammatory mediators interleukin-6 (IL-6, 30.4 %), monocyte chemoattractant protein-1 (MCP-1, 25.2 %), and increased adiponectin (33.7 %) compared to HF-fed mice. Expression of pro-inflammatory genes (Il6, Il12b, Nos2, and Emr1) in the stromal vascular fraction (SVF) of the epididymal white adipose tissue (WAT) was significantly reduced (37–56 %) in the cocoa-supplemented mice.


Dietary supplementation with cocoa ameliorates obesity-related inflammation, insulin resistance, and fatty liver disease in HF-fed obese mice, principally through the down-regulation of pro-inflammatory gene expression in WAT. These effects appear to be mediated in part by a modulation of dietary fat absorption and inhibition of macrophage infiltration in WAT.


Theobroma cacao Cocoa Polyphenols Inflammation Obesity 



Alanine aminotransferase


Adipose tissue-associated macrophage


Degree of polymerization


High fat


High-fat diet supplemented with 8 % cocoa powder


Homeostasis model assessment of insulin resistance




Inducible nitric oxide synthase


Low fat


Monocyte chemoattractant protein-1


Nitric oxide


Obesity-related fatty liver disease




Stromal vascular fraction


Tumor necrosis factor-α


White adipose tissue



The authors would like to acknowledge Dr. Sarah Forester, Ms. Sudathip Sae-tan, Ms. Tongtong Xu, Ms. Ling Tao, Mr. Zachary Bitzer, and Ms. Amy Brownschidle for technical assistance.

Conflict of interest


Supplementary material

394_2013_510_MOESM1_ESM.tif (92 kb)
Supplementary material 1 (TIFF 92 kb)


  1. 1.
    González-Castejón M, Rodriguez-Casado A (2011) Dietary phytochemicals and their potential effects on obesity: a review. Pharmacol Res 64:438–455CrossRefGoogle Scholar
  2. 2.
    Finkelstein EA, Khavjou OA, Thompson H, Trogdon JG, Pan L, Sherry B, Dietz W (2012) Obesity and severe obesity forecasts through 2030. Am J Prev Med 42:563–570CrossRefGoogle Scholar
  3. 3.
    Terra X, Pallarés V, Ardèvol A, Bladé C, Fernández-Larrea J, Pujadas G, Salvadó J, Arola L, Blay M (2011) Modulatory effect of grape-seed procyanidins on local and systemic inflammation in diet-induced obesity rats. J Nutr Biochem 22:380–387CrossRefGoogle Scholar
  4. 4.
    Emanuela F, Grazia M, Marco DR, Maria Paola L, Giorgio F, Marco B (2012) Inflammation as a link between obesity and metabolic syndrome. J Nutr Metab 2012:476380CrossRefGoogle Scholar
  5. 5.
    Wellen KE, Hotamisligil GS (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 112:1785–1788Google Scholar
  6. 6.
    Terra X, Montagut G, Bustos M, Llopiz N, Ardèvol A, Bladé C, Fernández-Larrea J, Pujadas G, Salvadó J, Arola L, Blay M (2009) Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J Nutr Biochem 20:210–218CrossRefGoogle Scholar
  7. 7.
    Kanamoto Y, Yamashita Y, Nanba F, Yoshida T, Tsuda T, Fukuda I, Nakamura-Tsuruta S, Ashida H (2011) A black soybean seed coat extract prevents obesity and glucose intolerance by up-regulating uncoupling proteins and down-regulating inflammatory cytokines in high-fat diet-fed mice. J Agric Food Chem 59:8985–8993CrossRefGoogle Scholar
  8. 8.
    Weisberg SP, Mccann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808Google Scholar
  9. 9.
    Khandekar MJ, Cohen P, Spiegelman BM (2011) Molecular mechanisms of cancer development in obesity. Nat Rev Cancer 11:886–895CrossRefGoogle Scholar
  10. 10.
    Eder K, Baffy N, Falus A (2009) The major inflammatory mediator interleukin-6 and obesity. Inflamm Res 58:727–736CrossRefGoogle Scholar
  11. 11.
    Clément S, Juge-Aubry C, Sgroi A, Conzelmann S, Pazienza V, Pittet-Cuenod B, Meier CA, Negro F (2008) Monocyte chemoattractant protein-1 secreted by adipose tissue induces direct lipid accumulation in hepatocytes. Hepatol 48:799–807CrossRefGoogle Scholar
  12. 12.
    Grassi D, Necozione S, Lippi C, Croce G, Valeri L, Pasqualetti P, Desideri G, Blumberg JB, Ferri C (2005) Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension 46:398–405CrossRefGoogle Scholar
  13. 13.
    Selmi C, Mao TK, Keen CL, Schmitz HH, Gershwin ME (2006) The anti-inflammatory properties of cocoa flavanols. Inflammation 47:163–171Google Scholar
  14. 14.
    Cooper KA, Donovan JL, Waterhouse AL, Williamson G (2008) Cocoa and health: a decade of research. Br J Nutr 99:1–11CrossRefGoogle Scholar
  15. 15.
    Monagas M, Khan N, Andres-Lacueva C, Casas R, Urpí-Sardà M, Llorach R, Lamuela-Raventós RM, Estruch R (2009) Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease. Am J Clin Nutr 90:1144–1150CrossRefGoogle Scholar
  16. 16.
    Ruzaidi A, Amin I, Nawalyah AG, Hamid M, Faizul HA (2005) The effect of Malaysian cocoa extract on glucose levels and lipid profiles in diabetic rats. J Ethnopharmacol 98:55–60CrossRefGoogle Scholar
  17. 17.
    Matsui N, Ito R, Nishimura E, Yoshikawa M, Kato M, Kamei M, Shibata H, Matsumoto I, Abe K, Hashizume S (2005) Ingested cocoa can prevent high-fat diet-induced obesity by regulating the expression of genes for fatty acid metabolism. Nutrition 21:594–601CrossRefGoogle Scholar
  18. 18.
    Tomaru M, Takano H, Osakabe N, Yasuda A, Inoue K, Yanagisawa R, Ohwatari T, Uematsu H (2007) Dietary supplementation with cacao liquor proanthocyanidins prevents elevation of blood glucose levels in diabetic obese mice. Nutrition 23:351–355CrossRefGoogle Scholar
  19. 19.
    Jalil AMM, Ismail A, Pei CP, Hamid M, Kamaruddin SHS (2008) Effects of cocoa extract on glucometabolism, oxidative stress, and antioxidant enzymes in obese-diabetic (Ob-db) rats. J Agric Food Chem 56:7877–7884CrossRefGoogle Scholar
  20. 20.
    Yamashita Y, Okabe M, Natsume M, Ashida H (2012) Prevention mechanisms of glucose intolerance and obesity by cacao liquor procyanidin extract in high-fat diet-fed C57BL/6 mice. Arch Biochem Biophys 2012:1–10Google Scholar
  21. 21.
    Mao T, Water JVD, Keen CL, Schmitz HH, Gershwin ME (2000) Cocoa Procyanidins and Human Cytokine Transcription and Secretion. J Nutr 130:2093–2099Google Scholar
  22. 22.
    Mao TK, Powell J, Water JVD, Keen CL, Schmitz HH, John F, Gershwin ME (2000) The Effect of cocoa procyanidins on the transcription and secretion of interleukin 1beta in peripheral blood mononuclear cells. Life Sci 66:1377–1386CrossRefGoogle Scholar
  23. 23.
    Mao TK, van de Water J, Keen CL, Schmitz HH, Gershwin ME (2002) Modulation of TNF-α secretion in peripheral blood mononuclear cells by cocoa flavanols and procyanidins. Dev Immunol 9:135–141CrossRefGoogle Scholar
  24. 24.
    Ramiro E, Franch A, Castellote C, Pérez-Cano F, Permanyer J, Izquierdo-Pulido M, Castell M (2005) Flavonoids from theobroma cacao down-regulate inflammatory mediators. J Agric Food Chem 53:8506–8511CrossRefGoogle Scholar
  25. 25.
    Kenny TP, Keen CL, Schmitz HH, Gershwin ME, Enny THPK, Een CARLLK, Chmitz HAHS (2007) Immune effects of procyanidin oligomers on peripheral blood mononuclear cells. Exp Biol Med 232:293–300Google Scholar
  26. 26.
    Gu Y, Hurst WJ, Stuart DA, Lambert JD (2011) Inhibition of key digestive enzymes by cocoa extracts and procyanidins. J Agric Food Chem 59:5305–5311CrossRefGoogle Scholar
  27. 27.
    Kelm MA, Johnson JC, Robbins RJ, Hammerstone JF, Schmitz HH (2006) High-performance liquid chromatography separation and purification of cacao (Theobroma cacao L.) procyanidins according to degree of polymerization using a diol stationary phase. J Agric Food Chem 54:1571–1576CrossRefGoogle Scholar
  28. 28.
    Mlinar B, Marc J, Janez A, Peifer M (2007) Molecular mechanisms of insulin resistance and associated diseases. Clin Chim Acta 375:20–35CrossRefGoogle Scholar
  29. 29.
    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 112:1821–1830Google Scholar
  30. 30.
    Lumeng CN, Deyoung SM, Bodzin JL, Saltiel AR (2007) Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 56:16–23CrossRefGoogle Scholar
  31. 31.
    Trayhurn P, Wood IS (2005) Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans 33:1078–1081CrossRefGoogle Scholar
  32. 32.
    Grassi D, Lippi C, Necozione S, Desideri G, Ferri C (2005) Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr 81:611–614Google Scholar
  33. 33.
    de Luca C, Olefsky JM (2008) Inflammation and insulin resistance. FEBS Lett 582:97–105CrossRefGoogle Scholar
  34. 34.
    Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Invest 116:1793–1801CrossRefGoogle Scholar
  35. 35.
    Olefsky JM, Glass CK (2010) Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72:219–246CrossRefGoogle Scholar
  36. 36.
    Clark J, Brancati F, Diehl A (2003) The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 98:960–967CrossRefGoogle Scholar
  37. 37.
    Schindhelm RK, Diamant M, Dekker JM, Teerlink T, Heine RJ (2006) Alanine aminotransferase as a marker of non-alcoholic fatty liver disease in relation to type 2 diabetes mellitus and cardiovascular disease. Diabetes Metab Res Rev 22:437–443CrossRefGoogle Scholar
  38. 38.
    Buechler C, Wanninger J, Neumeier M (2011) Adiponectin, a key adipokine in obesity related liver diseases. World J Gastroenterol 17:2801–28011Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Center of Excellence for Plant and Mushroom Foods and Health, Department of Food ScienceThe Pennsylvania State UniversityUniversity ParkUSA
  2. 2.Department of Veterinary and Biomedical Sciences, Intercollege Graduate Program in PhysiologyThe Pennsylvania State UniversityUniversity ParkUSA

Personalised recommendations