A Low Dose of Dietary Quercetin Fails to Protect against the Development of an Obese Phenotype in Mice

Abstract

The purpose of this study was to examine the effect of a 40% high-fat diet (HFD) supplemented with a dietary attainable level of quercetin (0.02%) on body composition, adipose tissue (AT) inflammation, Non-Alcoholic Fatty-Liver Disease (NAFLD), and metabolic outcomes. Diets were administered for 16 weeks to C57BL/6J mice (n = 10/group) beginning at 4 weeks of age. Body composition and fasting blood glucose, insulin, and total cholesterol concentrations were examined intermittently. AT and liver mRNA expression (RT-PCR) of inflammatory mediators (F4/80, CD206 (AT only), CD11c (AT only) TLR-2 (AT only), TLR-4 (AT only), MCP-1, TNF-α, IL-6 (AT only), and IL-10 (AT only)) were measured along with activation of NFκB-p65, and JNK (western blot). Hepatic lipid accumulation, gene expression (RT-PCR) of hepatic metabolic markers (ACAC1, SREBP-1, PPAR-γ), protein content of Endoplasmic Reticulum (ER) Stress markers (BiP, phosphorylated and total EIF2α, phosphorylated and total IRE1α, CHOP), and hepatic oxidative capacity were assessed (western blot). Quercetin administration had no effect at mitigating increases in visceral AT, AT inflammation, hepatic steatosis, ER Stress, decrements in hepatic oxidative capacity, or the development of insulin resistance and hypercholesterolemia. In conclusion, 0.02% quercetin supplementation is not an effective therapy for attenuating HFD-induced obesity development. It is likely that a higher dose of quercetin supplementation is needed to elicit favorable outcomes in obesity.

miR155 deficiency aggravates high-fat diet-induced adipose tissue fibrosis in male mice

“…) and we have previously found JNK phosphorylation to be elevated in the adipose tissue of mice consuming the same HFD utilized in this experiment (Enos et al. , , ; Cranford et al. ).…”

“…It should be noted that an attempt was made to examine adipose tissue macrophage infiltration (F4/80 immunohistochemistry) in order to corroborate the qRT‐PCR data as in our previous publications (Enos et al. , , ). However, due to unspecific positive staining as a result of the elevated adipose tissue fibrosis exhibited by the mir155 −/− HFD mice, we were unable to accurately assess macrophage infiltration by immunohistochemistry.…”

“…For example, the diet utilized in this study was designed to be similar to the standard American diet and has been previously used in other investigations (Enos et al. , ,b, ). This diet is different than the majority of other HFDs utilized in obesity investigations as typical HFD diets tend to be much higher in total (approximately 60% in some cases) and saturated fat (up to 25%).…”

“…After completion of the western blot, all membranes were stained with Amido black, and the densitometry of each lane was calculated, using Quantity One Software (BioRad, Hercules, CA) allowing for total protein normalization as previously described (Enos et al. ). This method of normalization has been shown to be more accurate than typically used loading controls (Aldridge et al.…”

Mice Fed a High‐Cholesterol Diet Supplemented with Quercetin‐3‐Glucoside Show Attenuated Hyperlipidemia and Hyperinsulinemia Associated with Differential Regulation of PCSK9 and LDLR in their Liver and Pancreas

“…Some studies have shown that dietary quercetin can reduce diet‐induced obesity; others have not . Difference in diets as well as quercetin molecular forms, dosage, and duration of treatment could explain these discrepancies.…”