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

Abstract

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.

Figures

Fig. 1

Plasma quercetin concentration in samples taken from mice at the zenith (1:00 am, night) and nadir (1 pm, day) of the metabolic cycle after consuming a high-fat diet (45 kcal%) containing 0.80% quercetin for 3W or 8W. Quercetin was measured by MS as described in Methods. Means were calculated from 3 to 4 mice sampled at each time of day and time on diet and compared by ANOVA. Means with different letters differ at P < .05.

Fig. 2

Change in food consumption (kilocalories per day) over time in mice provided high-fat diets (45 kcal %) containing either vehicle (HF) or 0.8% quercetin (HF + Q). Food consumption, accounting for spillage, was measured over a 2-day period each week for 32 mice per diet from 0 to 3W and 16 mice per diet from 4 to 8W. Means were compared by 2-way ANOVA as described in Methods to test for diet-dependent differences in food consumption each week. Mean food consumption did not differ between the diets at any week during the study.

Fig. 3

Change in body weight over time in mice provided high-fat diets (45 kcal%) containing either vehicle (HF) or 0.8% quercetin (HF + Q). Means were compared by 2-way ANOVA as described in Methods to test for diet-dependent differences in body weight each week. Mean body weight did not differ between the groups at any week during the study.

Fig. 4

Change in FM as a percentage of body weight over time in mice provided high-fat diets (45 kcal %) containing either vehicle (HF) or 0.8% quercetin (HF + Q). Body composition was determined each week by NMR as described in Methods, and FM was expressed as a percentage of body weight to measure relative adiposity. Means were compared by 2-way ANOVA to test for diet-dependent differences in adiposity at each week. Mean adiposity did not differ between the 2 groups at any week during the study.

Fig. 5

Energy expenditure (kilojoules per hour per FFM) was measured by indirect calorimetry in mice after 3W (A) or 8W (B) on the respective HF (n = 8) or HF + Q (n = 8) diets. Mean EEs during the night and day intervals were compared between diets at 3 and 8W using 2-way ANOVA as described in Methods. Mean EE during the night at 3W and during the day and night at 8W did not differ between dietary groups, but mean EE during the day at 3W was significantly higher (P < .05) in the HF + Q compared with the HF group. (C) Oxygen consumption and CO2 production were measured continuously at 45-minute intervals for 3 days by indirect calorimetry in mice after 3 and 8W on the respective HF (n = 8) or HF + Q (n = 8) diets. Respiratory quotients were calculated as the ratio of CO2 produced vs O2 consumed, and mean RQs were obtained from the measurements taken between 7:00 pm and 7:00 am (night) and between 7:00 am and 7:00 pm (day). Mean day and night RQs determined after 3 and 8W on the respective diets were compared using 2-way ANOVA as described in Methods. Mean RQs did not differ between diets and between time of day, and no time of day × diet interaction was detected.

Fig. 6

Plasma cytokine concentrations in mice after 8W on the respective HF (n = 6) or HF + Q (n = 6) diets. Mean plasma concentrations of each cytokine were compared between diets using 1-way ANOVA as described in Methods. Means denoted with an asterisk differ at P < .05.