DOI QR코드

DOI QR Code

Dietary Aloe Reduces Adipogenesis via the Activation of AMPK and Suppresses Obesity-related Inflammation in Obese Mice

  • 투고 : 2011.03.17
  • 심사 : 2011.03.31
  • 발행 : 2011.04.30

초록

Background: Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results: Aloe QDM complex downregulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-$1{\beta}$ and -6) and $HIF1{\alpha}$ mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-${\kappa}B$ p65 from the cytosol in the WAT. Conclusion: Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.

키워드

참고문헌

  1. Rajala MW, Scherer PE: Minireview: The adipocyte--at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144;3765-3773, 2003 https://doi.org/10.1210/en.2003-0580
  2. Wellen KE, Hotamisligil GS: Inflammation, stress, and diabetes. J Clin Invest 115;1111-1119, 2005
  3. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr: Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112;1796-1808, 2003
  4. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H: Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112;1821-1830, 2003
  5. Hardie DG, Carling D: The AMP-activated protein kinase--fuel gauge of the mammalian cell? Eur J Biochem 246;259-273, 1997 https://doi.org/10.1111/j.1432-1033.1997.00259.x
  6. Sag D, Carling D, Stout RD, Suttles J: Adenosine 5'-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype. J Immunol 181;8633-8641, 2008
  7. Makinde AO, Gamble J, Lopaschuk GD: Upregulation of 5'-AMP-activated protein kinase is responsible for the increase in myocardial fatty acid oxidation rates following birth in the newborn rabbit. Circ Res 80;482-489, 1997 https://doi.org/10.1161/01.RES.80.4.482
  8. Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI: AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A 99;15983-15987, 2002 https://doi.org/10.1073/pnas.252625599
  9. Ju JS, Gitcho MA, Casmaer CA, Patil PB, Han DG, Spencer SA, Fisher JS: Potentiation of insulin-stimulated glucose transport by the AMP-activated protein kinase. Am J Physiol Cell Physiol 292;C564-572, 2007
  10. Iglesias MA, Ye JM, Frangioudakis G, Saha AK, Tomas E, Ruderman NB, Cooney GJ, Kraegen EW: AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats. Diabetes 51;2886-2894, 2002 https://doi.org/10.2337/diabetes.51.10.2886
  11. Shin E, Shim KS, Kong H, Lee S, Shin S, Kwon J, Jo TH, Park YI, Lee CK, Kim K: Dietary Aloe Improves Insulin Sensitivity via the Suppression of Obesity-induced Inflammation in Obese Mice. Immune Netw 11;59-67, 2011 https://doi.org/10.4110/in.2011.11.1.59
  12. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature 409;307-312, 2001 https://doi.org/10.1038/35053000
  13. 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 436;356-362, 2005 https://doi.org/10.1038/nature03711
  14. Olefsky JM, Glass CK: Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72:219-246, 2010 https://doi.org/10.1146/annurev-physiol-021909-135846
  15. Mertzw W, Schwarz K: Relation of glucose tolerance factor to impaired intravenous glucose tolerance of rats on stock diets. Am J Physiol 196;614-618, 1959
  16. Schwarz K, Mertz W: Chromium(III) and the glucose tolerance factor. Arch Biochem Biophys 85:292-295, 1959 https://doi.org/10.1016/0003-9861(59)90479-5
  17. Anderson RA: Recent advances in the clinical and biochemical effects of chromium deficiency. Prog Clin Biol Res 380:221-234, 1993
  18. Mertz W: Chromium in human nutrition: a review. J Nutr 123;626-633, 1993
  19. Anderson RA: Chromium, glucose intolerance and diabetes. J Am Coll Nutr 17;548-555, 1998 https://doi.org/10.1080/07315724.1998.10718802
  20. Kim K, Kim H, Kwon J, Lee S, Kong H, Im SA, Lee YH, Lee YR, Oh ST, Jo TH, Park YI, Lee CK, Kim K: Hypoglycemic and hypolipidemic effects of processed Aloe vera gel in a mouse model of non-insulin-dependent diabetes mellitus. Phytomedicine 16;856-863, 2009 https://doi.org/10.1016/j.phymed.2009.02.014
  21. Kong HS, Lee SW, Shin SM, Kwon JH, Jo TH, Shin EJ, Shim KS, Park YI, Lee CK, Kim KJ: Down-regulation of adipogenesis and hyperglycemia in diet-induced obesity mouse model by aloe QDM. Biomolecules & Therapeutics 18;336-342, 2010 https://doi.org/10.4062/biomolther.2010.18.3.336
  22. Kim JO, Kim KS, Lee GD, Kwon JH: Antihyperglycemic and antioxidative effects of new herbal formula in streptozotocin-induced diabetic rats. J Med Food 12;728-735, 2009 https://doi.org/10.1089/jmf.2008.1195
  23. Martin-Fuentes P, Civeira F, Recalde D, Garcia-Otin AL, Jarauta E, Marzo I, Cenarro A: Individual variation of scavenger receptor expression in human macrophages with oxidized low-density lipoprotein is associated with a differential inflammatory response. J Immunol 179;3242-3248, 2007
  24. Sahoo D, Drover V: The role of scavenger receptors in signaling, inflammation and atherosclerosis. Biochemistry of Atherosclerosis 1;70-91, 2006
  25. Peiser L, Gordon S: The function of scavenger receptors expressed by macrophages and their role in the regulation of inflammation. Microbes Infect 3;149-159, 2001 https://doi.org/10.1016/S1286-4579(00)01362-9
  26. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, Lacy-Hulbert A, El Khoury J, Golenbock DT, Moore KJ: CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol 11;155-161, 2010 https://doi.org/10.1038/ni.1836
  27. Hoebe K, Georgel P, Rutschmann S, Du X, Mudd S, Crozat K, Sovath S, Shamel L, Hartung T, Zähringer U, Beutler B: CD36 is a sensor of diacylglycerides. Nature 433;523-527, 2005 https://doi.org/10.1038/nature03253
  28. Stuart LM, Deng J, Silver JM, Takahashi K, Tseng AA, Hennessy EJ, Ezekowitz RA, Moore KJ: Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain. J Cell Biol 170;477-485, 2005 https://doi.org/10.1083/jcb.200501113
  29. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS: TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116;3015-3025, 2006 https://doi.org/10.1172/JCI28898
  30. Tsukumo DM, Carvalho-Filho MA, Carvalheira JB, Prada PO, Hirabara SM, Schenka AA, Araujo EP, Vassallo J, Curi R, Velloso LA, Saad MJ: Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 56;1986-1998, 2007 https://doi.org/10.2337/db06-1595
  31. Regazzetti C, Peraldi P, Gremeaux T, Najem-Lendom R, Ben-Sahra I, Cormont M, Bost F, Le Marchand-Brustel Y, Tanti JF, Giorgetti-Peraldi S: Hypoxia decreases insulin signaling pathways in adipocytes. Diabetes 58;95-103, 2009 https://doi.org/10.2337/db08-0457
  32. Trayhurn P, Wang B, Wood IS: Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity? Br J Nutr 100;:227-235, 2008
  33. Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot JL, Bouloumie A, Barbatelli G, Cinti S, Svensson PA, Barsh GS, Zucker JD, Basdevant A, Langin D, Clement K: Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 54;2277-2286, 2005 https://doi.org/10.2337/diabetes.54.8.2277

피인용 문헌

  1. Energy dysfunction in Huntington’s disease: insights from PGC-1α, AMPK, and CKB vol.69, pp.24, 2011, https://doi.org/10.1007/s00018-012-1025-2
  2. UP780, a Chromone-Enriched <i>Aloe</i> Composition, Enhances Adipose Insulin Receptor Signaling and Decreases Liver Lipid Biosynthesis vol.3, pp.2, 2011, https://doi.org/10.4236/ojgen.2013.32a2002
  3. The Synergy Effect of Weight-Bearing Circuit Training and Aloe QDM Complex on Obese Middle Aged Women: a Randomized Double-Blind Controlled Trial vol.14, pp.2, 2011, https://doi.org/10.15384/kjhp.2014.14.2.59
  4. Efficacy of Aloe Vera Supplementation on Prediabetes and Early Non-Treated Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials vol.8, pp.7, 2011, https://doi.org/10.3390/nu8070388
  5. Reduction of Fasting Blood Glucose and Hemoglobin A1c Using Oral Aloe Vera: A Meta-Analysis vol.22, pp.6, 2016, https://doi.org/10.1089/acm.2015.0122
  6. Screening of exosomal miRNAs derived from subcutaneous and visceral adipose tissues: Determination of targets for the treatment of obesity and associated metabolic disorders vol.18, pp.3, 2011, https://doi.org/10.3892/mmr.2018.9312
  7. Aloe vera as an herbal medicine in the treatment of metabolic syndrome: A review vol.33, pp.10, 2011, https://doi.org/10.1002/ptr.6465
  8. Medicinal plants and phytochemicals for diabetes mellitus: pharmacokinetic characteristics and herb-drug interactions vol.49, pp.6, 2019, https://doi.org/10.1007/s40005-019-00440-4
  9. Natural Bioactive Compounds Useful in Clinical Management of Metabolic Syndrome vol.13, pp.2, 2021, https://doi.org/10.3390/nu13020630
  10. Modulation of Pro-inflammatory and Anti-inflammatory Cytokines in the Fat by an Aloe Gel-based Formula, QDMC, Is Correlated with Altered Gut Microbiota vol.21, pp.2, 2011, https://doi.org/10.4110/in.2021.21.e15
  11. The Role of Poly-Herbal Extract in Sodium Chloride-Induced Oxidative Stress and Hyperlipidemia in Male Wistar Rats vol.8, pp.6, 2011, https://doi.org/10.3390/medicines8060025