Quercetin transiently increases energy expenditure but persistently decreases circulating markers of inflammation in C57BL/6J mice fed a high-fat diet.

Quercetin, a polyphenolic compound and a major bioflavonoid in the human diet, has anti-inflammatory properties and has been postulated to enhance energy expenditure (EE). We sought to determine whether quercetin alters body weight, body composition, EE, and circulating markers of inflammation. At 6 weeks (W) of age, 2 cohorts of C57BL/6J mice (N = 80) were placed on one of 2 diets for 3W or 8W: (1) high fat (HF) (45% kcal fat) or (2) high fat + quercetin (HF + Q) (45% kcal fat + 0.8% quercetin). Quercetin concentrations in the diet and plasma were evaluated using mass spectrometry. Body weight, composition (nuclear magnetic resonance), and food consumption were measured weekly. Energy expenditure was measured by indirect calorimetry at 3 and 8W, and inflammatory markers were measured in plasma obtained at 8W. The presence of quercetin in the HF diet did not alter food consumption over time in the HF + Q group and did not differ from the HF group at any time point. However, circulating plasma quercetin concentrations declined between 3 and 8W. At 3W, EE was higher during both day and night phases (P < .0001) in the HF + Q group compared with the HF group; but this difference was not detected at 8W and did not translate into significant differences between the HF + Q and HF groups with respect to body weight or body composition. During the night phase, concentrations of the inflammatory markers (interferon-gamma, interleukin-1alpha, and interleukin-4) were significantly lower when compared with HF treatment group (P < .05). Dietary supplementation with quercetin produces transient (3W) increases in EE that are not detected after 8W on the diet. A corresponding decrease in circulating quercetin between 3 and 8W suggests that metabolic adaptation may have diminished the impact of quercetin's early effect on EE and diminished its overall effect on nutrient partitioning and adiposity. However, quercetin at the levels provided was effective in reducing circulating markers of inflammation observed in animals on an HF diet at 8W.

[1]  R. Bruno,et al.  A quercetin supplemented diet does not prevent cardiovascular complications in spontaneously hypertensive rats. , 2007, The Journal of nutrition.

[2]  Juan Li,et al.  The inhibitory effect of quercetin on IL-6 production by LPS-stimulated neutrophils. , 2005, Cellular & molecular immunology.

[3]  D. Gómez-Coronado,et al.  Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinflammatory effects in both hemodialysis patients and healthy subjects. , 2006, The American journal of clinical nutrition.

[4]  K. Jeong,et al.  Quercetin suppresses proinflammatory cytokines production through MAP kinases and NF-κB pathway in lipopolysaccharide-stimulated macrophage , 2004, Molecular and Cellular Biochemistry.

[5]  Yukiko Yamamoto,et al.  Antihypertensive Effect of Quercetin in Rats Fed with a High-Fat High-Sucrose Diet , 2006, Bioscience, biotechnology, and biochemistry.

[6]  J. Harney,et al.  The Small Polyphenolic Molecule Kaempferol Increases Cellular Energy Expenditure and Thyroid Hormone Activation , 2007, Diabetes.

[7]  H. Aeschbacher,et al.  Nonmutagenicity in vivo of the food flavonol quercetin. , 1982, Nutrition and cancer.

[8]  S. Dower,et al.  Evidence that MAP (mitogen-activated protein) kinase activation may be a necessary but not sufficient signal for a restricted subset of responses in IL-1-treated epidermoid cells. , 1992, Cytokine.

[9]  I. Raskin,et al.  Bioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus. , 2006, Phytochemistry.

[10]  J. E. Silva,et al.  Thermogenic mechanisms and their hormonal regulation. , 2006, Physiological reviews.

[11]  M. Comalada,et al.  Intestinal anti-inflammatory activity of combined quercitrin and dietary olive oil supplemented with fish oil, rich in EPA and DHA (n-3) polyunsaturated fatty acids, in rats with DSS-induced colitis. , 2006, Clinical nutrition.

[12]  M B Katan,et al.  Bioavailability and health effects of dietary flavonols in man. , 1998, Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement.

[13]  TonyHayek,et al.  Reduced Progression of Atherosclerosis in Apolipoprotein E–Deficient Mice Following Consumption of Red Wine, or Its Polyphenols Quercetin or Catechin, Is Associated With Reduced Susceptibility of LDL to Oxidation and Aggregation , 1997 .

[14]  D. Lamson,et al.  Antioxidants and cancer, part 3: quercetin. , 2000, Alternative medicine review : a journal of clinical therapeutic.

[15]  S. Wolffram,et al.  Bioavailability of quercetin in pigs is influenced by the dietary fat content. , 2004, The Journal of nutrition.

[16]  J. González‐Gallego,et al.  Evaluation of the genotoxic effect of rutin and quercetin by comet assay and micronucleus test. , 2002, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[17]  M. R. Peluso Flavonoids Attenuate Cardiovascular Disease, Inhibit Phosphodiesterase, and Modulate Lipid Homeostasis in Adipose Tissue and Liver , 2006, Experimental biology and medicine.

[18]  C. Swanson Suggested guidelines for articles about botanical dietary supplements. , 2002, The American journal of clinical nutrition.

[19]  R. Kapur,et al.  Quercetin, an Over-the-Counter Supplement, Causes Neuroblastoma-like Elevation of Plasma Homovanillic Acid , 2003, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[20]  F. Pi‐Sunyer A review of long-term studies evaluating the efficacy of weight loss in ameliorating disorders associated with obesity. , 1996, Clinical therapeutics.

[21]  E. Urdaneta,et al.  Effect of dietary quercetin and sphingomyelin on intestinal nutrient absorption and animal growth , 2006, British Journal of Nutrition.

[22]  M. Rhee,et al.  Radical scavenging and anti‐inflammatory activity of extracts from Opuntia humifusa Raf. , 2006, The Journal of pharmacy and pharmacology.

[23]  J. González‐Gallego,et al.  Quercetin decreases oxidative stress, NF-kappaB activation, and iNOS overexpression in liver of streptozotocin-induced diabetic rats. , 2005, The Journal of nutrition.

[24]  J. Farmer,et al.  Obesity and inflammation: A new look at an old problem , 2007, Current atherosclerosis reports.

[25]  L. Misiak,et al.  Modification of membranes by quercetin, a naturally occurring flavonoid, via its incorporation in the polar head group. , 2007, Biochimica et biophysica acta.

[26]  M. Comalada,et al.  In vivo quercitrin anti‐inflammatory effect involves release of quercetin, which inhibits inflammation through down‐regulation of the NF‐κB pathway , 2005, European journal of immunology.

[27]  Paul E Milbury,et al.  Flavonols, flavones, flavanones, and human health: epidemiological evidence. , 2005, Journal of medicinal food.

[28]  J. Tamargo,et al.  Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats , 2001, British journal of pharmacology.

[29]  E. Stylianou,et al.  Bioflavonoid quercetin inhibits interleukin-1-induced transcriptional expression of monocyte chemoattractant protein-1 in glomerular cells via suppression of nuclear factor-kappaB. , 1999, Journal of the American Society of Nephrology : JASN.

[30]  M. Yamasaki,et al.  Mulberry (Morus alba L.) leaves and their major flavonol quercetin 3-(6-malonylglucoside) attenuate atherosclerotic lesion development in LDL receptor-deficient mice. , 2005, The Journal of nutrition.

[31]  Gary Williamson,et al.  Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. , 2005, The American journal of clinical nutrition.

[32]  H. Ohgaki,et al.  Carcinogenicity test of quercetin and rutin in golden hamsters by oral administration. , 1982, Carcinogenesis.