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Kaempferol Ameliorates Metabolic Syndrome by Inhibiting Inflammation and Oxidative Stress in High-Fat Diet-Induced Obese Mice

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AbstractBACKGROUND/OBJECTIVESKaempferol (Ka) is one of the most widely occurring flavonoids found in large amounts in various plants. Ka has anti-obesity, antioxidant, and anti-inflammatory effects. Despite the numerous papers documenting the efficacy of Ka, some controversy remains. Therefore, this study examined the impact of Ka using 3T3-L1 and high-fat diet-induced obese mice. MATERIALS/METHODS3T3-L1 cells were treated with 50 μM Ka from the initiation of 3T3-L1 differentiation at D0 until the completion of differentiation on D8. Thirty male mice (C57BL/6J, 4 weeks old) were divided into 3 groups: normal diet (ND), high-fat diet (HFD), and HFD + 0.02% (w/w) Ka (Ka) group. All mice were fed their respective diets ad libitum for 16 weeks. The mice were sacriced, and the plasma and hepatic lipid levels, white adipose tissue weight, hepatic glucose level, lipid level, and antioxidant enzyme activities were analyzed, and immunohistochemistry staining was performed. RESULTSKa suppressed the hypertrophy of 3T3-L1 cells, and the Ka-supplemented mice showed a significant decrease in perirenal, retroperitoneal, mesenteric, and subcutaneous fat compared to the HFD group. Ka supplementation in high-fat diet-induced obese mice also improved the overall blood lipid concentration (total cholesterol, non-high-density lipoprotein-cholesterol, phospholipids, and apolipoprotein B). Ka supplementation in high-fat-induced obesity mice reduced hepatic steatosis and insulin resistance by modulating the hepatic lipid (glucose-6-phosphate dehydrogenase, fatty acid synthase, malic enzyme, phosphatidate phosphohydrolase, and β-oxidation) activities and glucose (glucokinase, phosphoenolpyruvate carboxykinase, and G6pase)-regulating enzymes. Ka supplementation ameliorated the erythrocyte and hepatic mitochondrial H2O2 and inflammation levels (plasma tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6, and interferon-gamma and fibrosis of liver and epididymal fat). CONCLUSIONKa may be beneficial for preventing diet-induced obesity, inflammation, oxidative stress, and diabetes.

Abstract

AbstractBACKGROUND/OBJECTIVESKaempferol (Ka) is one of the most widely occurring flavonoids found in large amounts in various plants. Ka has anti-obesity, antioxidant, and anti-inflammatory effects. Despite the numerous papers documenting the efficacy of Ka, some controversy remains. Therefore, this study examined the impact of Ka using 3T3-L1 and high-fat diet-induced obese mice. MATERIALS/METHODS3T3-L1 cells were treated with 50 μM Ka from the initiation of 3T3-L1 differentiation at D0 until the completion of differentiation on D8. Thirty male mice (C57BL/6J, 4 weeks old) were divided into 3 groups: normal diet (ND), high-fat diet (HFD), and HFD + 0.02% (w/w) Ka (Ka) group. All mice were fed their respective diets ad libitum for 16 weeks. The mice were sacriced, and the plasma and hepatic lipid levels, white adipose tissue weight, hepatic glucose level, lipid level, and antioxidant enzyme activities were analyzed, and immunohistochemistry staining was performed. RESULTSKa suppressed the hypertrophy of 3T3-L1 cells, and the Ka-supplemented mice showed a significant decrease in perirenal, retroperitoneal, mesenteric, and subcutaneous fat compared to the HFD group. Ka supplementation in high-fat diet-induced obese mice also improved the overall blood lipid concentration (total cholesterol, non-high-density lipoprotein-cholesterol, phospholipids, and apolipoprotein B). Ka supplementation in high-fat-induced obesity mice reduced hepatic steatosis and insulin resistance by modulating the hepatic lipid (glucose-6-phosphate dehydrogenase, fatty acid synthase, malic enzyme, phosphatidate phosphohydrolase, and β-oxidation) activities and glucose (glucokinase, phosphoenolpyruvate carboxykinase, and G6pase)-regulating enzymes. Ka supplementation ameliorated the erythrocyte and hepatic mitochondrial H2O2 and inflammation levels (plasma tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6, and interferon-gamma and fibrosis of liver and epididymal fat). CONCLUSIONKa may be beneficial for preventing diet-induced obesity, inflammation, oxidative stress, and diabetes.

참고문헌 (51)

  1. Ng M, "Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013 : a systematic analysis for the Global Burden of Disease Study 2013", Lancet, 384, pp.766~781 (2014)
  2. Fried SK, "Omental and subcutaneous adipose tissues of obese subjects release interleukin-6 : depot difference and regulation by glucocorticoid", J Clin Endocrinol Metab, 83, pp.847~850 (1998)
  3. Shimomura I, "Enhanced expression of PAI-1 in visceral fat : possible contributor to vascular disease in obesity", Nat Med, 2, pp.800~803 (1996)
  4. Steppan CM, "The hormone resistin links obesity to diabetes", Nature, 409, pp.307~312 (2001)
  5. Kahn BB, "Obesity and insulin resistance", J Clin Invest, 106, pp.473~481 (2000)
  6. Shoelson SE, "Obesity, inflammation, and insulin resistance", Gastroenterology, 132, pp.2169~2180 (2007)
  7. Huang Cao ZF, "Role of perivascular adipose tissue in vascular physiology and pathology", Hypertension, 69, pp.770~777 (2017)
  8. Reho JJ, "Oxidative and inflammatory signals in obesity-associated vascular abnormalities", Clin Sci(Lond), 131, pp.1689~1700 (2017)
  9. Shah S, "Oxidative stress, glucose metabolism, and the prevention of type 2 diabetes : pathophysiological insights", Antioxid Redox Signal, 9, pp.911~929 (2007)
  10. Park K, "Oxidative stress and insulin resistance : the coronary artery risk development in young adults study", Diabetes Care, 32, pp.1302~1307 (2009)
  11. Jakubiak GK, ""Obesity and insulin resistance"is the component of the metabolic syndrome most strongly associated with oxidative stress", Antioxidants(Basel), 11, pp.79~ (2021)
  12. An G, "The bioflavonoid kaempferol is an Abcg2 substrate and inhibits Abcg2-mediated quercetin efflux", Drug Metab Dispos, 39, pp.426~432 (2011)
  13. Häkkinen SH, "Content of the flavonols quercetin, myricetin, and kaempferol in 25 edible berries", J Agric Food Chem, 47, pp.2274~2279 (1999)
  14. da-Silva WS, "The small polyphenolic molecule kaempferol increases cellular energy expenditure and thyroid hormone activation", Diabetes, 56, pp.767~776 (2007)
  15. Yu SF, "3-O-β-D-glucosyl-(1-->6)-β-D-glucosyl-kaempferol isolated from Sauropus androgenus reduces body weight gain in Wistar rats", Biol Pharm Bull, 29, pp.2510~2513 (2006)
  16. Lee YJ, "Kaempferol protects HIT-T15 pancreatic beta cells from 2-deoxy-D-ribose-induced oxidative damage", Phytother Res, 24, pp.419~423 (2010)
  17. Suh KS, "Kaempferol attenuates 2-deoxy-D-ribose-induced oxidative cell damage in MC3T3-E1 osteoblastic cells", Biol Pharm Bull, 32, pp.746~749 (2009)
  18. Crespo I, "A comparison of the effects of kaempferol and quercetin on cytokine-induced pro-inflammatory status of cultured human endothelial cells", Br J Nutr, 100, pp.968~976 (2008)
  19. Hämäläinen M, "Anti-inflammatory effects of flavonoids : genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-κB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-κB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages", Mediators Inflamm, 2007, pp.45673~ (2007)
  20. Ninomiya K, "Potent anti-obese principle from Rosa canina : structural requirements and mode of action of trans-tiliroside", Bioorg Med Chem Lett, 17, pp.3059~3064 (2007)
  21. Christensen KB, "Identification of bioactive compounds from flowers of black elder (Sambucus nigra L.) that activate the human peroxisome proliferator-activated receptor (PPAR) γ", Phytother Res, 24, pp.129~132 (2010)
  22. Carroll NV, "The determination of glycogen in liver and muscle by use of anthrone reagent", J Biol Chem, 220, pp.583~593 (1956)
  23. Davidson AL, "Factors underlying significant underestimations of glucokinase activity in crude liver extracts : physiological implications of higher cellular activity", Arch Biochem Biophys, 253, pp.156~167 (1987)
  24. Bentle LA, "Interaction of anions and divalent metal ions with phosphoenolpyruvate carboxykinase", J Biol Chem, 251, pp.2916~2921 (1976)
  25. Alegre M, "Determination of glucose-6-phosphatase activity using the glucose dehydrogenase-coupled reaction", Anal Biochem, 173, pp.185~189 (1988)
  26. Nepokroeff CM, "Fatty-acid synthase from rat liver", Methods Enzymol, 35, pp.37~44 (1975)
  27. Pitkänen E, "Enzymatic determination of unbound D-mannose in serum", Eur J Clin Chem Clin Biochem, 35, pp.761~766 (1997)
  28. Markwell MA, "The subcellular distribution of carnitine acyltransferases in mammalian liver and kidney. A new peroxisomal enzyme", J Biol Chem, 248, pp.3426~3432 (1973)
  29. Lazarow PB, "Assay of peroxisomal beta-oxidation of fatty acids", Methods Enzymol, 72, pp.315~319 (1981)
  30. Shapiro DJ, "Micro assay for 3-hydroxy-3-methylglutaryl-CoA reductase in rat liver and in L-cell fibroblasts", Biochim Biophys Acta, 370, pp.369~377 (1974)
  31. Gillies PJ, "Regulation of acyl-CoA : cholesterol acyltransferase activity in normal and atherosclerotic rabbit aortas : role of a cholesterol substrate pool", Exp Mol Pathol, 44, pp.329~339 (1986)
  32. Ohkawa H, "Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction", Anal Biochem, 95, pp.351~358 (1979)
  33. Marklund S, "Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase", Eur J Biochem, 47, pp.469~474 (1974)
  34. Aebi H, "Catalase in vitro", Methods Enzymol, 105, pp.121~126 (1984)
  35. Paglia DE, "Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase", J Lab Clin Med, 70, pp.158~169 (1967)
  36. Torres-Villarreal D, "Anti-obesity effects of kaempferol by inhibiting adipogenesis and increasing lipolysis in 3T3-L1 cells", J Physiol Biochem, 75, pp.83~88 (2019)
  37. Aguilera CM, "Alterations in plasma and tissue lipids associated with obesity and metabolic syndrome", Clin Sci(Lond), 114, pp.183~193 (2008)
  38. Pradhan A, "Obesity, metabolic syndrome, and type 2 diabetes : inflammatory basis of glucose metabolic disorders", Nutr Rev, 65, pp.S152~6 (2007)
  39. Saltiel AR, "Inflammatory mechanisms linking obesity and metabolic disease", J Clin Invest, 127, pp.1~4 (2017)
  40. Bian Y, "Kaempferol reduces obesity, prevents intestinal inflammation, and modulates gut microbiota in high-fat diet mice", J Nutr Biochem, 99, pp.108840~ (2022)
  41. Nainu F, "Natural products targeting inflammation-related metabolic disorders : a comprehensive review", Heliyon, 9, pp.e16919~ (2023)
  42. Picchi A, "Tumor necrosis factor-alpha induces endothelial dysfunction in the prediabetic metabolic syndrome", Circ Res, 99, pp.69~77 (2006)
  43. García-Ruiz I, "Uric acid and anti-TNF antibody improve mitochondrial dysfunction in ob", ob mice, 2006, pp.44, 581~591
  44. McCullough AJ, "Pathophysiology of nonalcoholic steatohepatitis", J Clin Gastroenterol (2006)
  45. Spranger J, "Inflammatory cytokines and the risk to develop type 2 diabetes : results of the prospective population-based European Prospective Investigation into Cancer and Nutrition(EPIC)-Potsdam Study", Diabetes, 52, pp.812~817 (2003)
  46. Bastard JP, "Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro", J Clin Endocrinol Metab, 87, pp.2084~2089 (2002)
  47. Juhan-Vague I, "Plasminogen activator inhibitor-1, inflammation, obesity, insulin resistance and vascular risk", J Thromb Haemost, 1, pp.1575~1579 (2003)
  48. Tarrats N, "Critical role of tumor necrosis factor receptor 1, but not 2, in hepatic stellate cell proliferation, extracellular matrix remodeling, and liver fibrogenesis", Hepatology, 54, pp.319~327 (2011)
  49. Martin S, "Caveolin-1 deficiency leads to increased susceptibility to cell death and fibrosis in white adipose tissue : characterization of a lipodystrophic model", PLoS One, 7, pp.e46242~ (2012)
  50. Arfian N, "Heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition", BMC Proc, 13, pp.17~ (2019)
  51. Chawla A, "Macrophage-mediated inflammation in metabolic disease", Nat Rev Immunol, 11, pp.738~749 (2011)

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