In vivo effects of dietary quercetin and quercetin-rich red onion extract on skeletal muscle mitochondria, metabolism, and insulin sensitivity

Abstract

Red onions and low doses of the flavonoid, quercetin, increase insulin sensitivity and improve glucose tolerance. We hypothesized that dietary supplementation with red onion extract (RO) would attenuate high fat diet (HFD)-induced obesity and insulin resistance similar to quercetin supplementation by increasing energy expenditure through a mechanism involving skeletal muscle mitochondrial adaptations. To test this hypothesis, C57BL/6J mice were randomized into four groups and fed either a low fat diet (LF), HFD (HF), HFD + quercetin (HF + Q), or HFD + RO (HF + RO) for 9 weeks. Food consumption and body weight and composition were measured weekly. Insulin sensitivity was assessed by insulin and glucose tolerance tests. Energy expenditure and physical activity were measured by indirect calorimetry. Skeletal muscle incomplete beta oxidation, mitochondrial number, and mtDNA-encoded gene expression were measured. Quercetin and RO supplementation decreased HFD-induced fat mass accumulation and insulin resistance (measured by insulin tolerance test) and increased energy expenditure; however, only HF + Q showed an increase in physical activity levels. Although quercetin and RO similarly increased skeletal muscle mitochondrial number and decreased incomplete beta oxidation, establishing mitochondrial function similar to that seen in LF, only HF + Q exhibited consistently lower mRNA levels of mtDNA-encoded genes necessary for complexes IV and V compared to LF. Quercetin- and RO-induced improvements in adiposity, insulin resistance, and energy expenditure occur through differential mechanisms, with quercetin-but not RO-induced energy expenditure being related to increases in physical activity. While both treatments improved skeletal muscle mitochondrial number and function, mtDNA-encoded transcript levels suggest that the antiobesogenic, insulin-sensitizing effects of purified quercetin aglycone, and RO may occur through differential mechanisms.

Skeletal Muscle Nucleo-Mitochondrial Crosstalk in Obesity and Type 2 Diabetes

“…Other studies support the conclusion that HFD feeding leads to obesity and insulin resistance, with decreased NEMG expression, impaired mitochondrial function and decreased mitochondrial number observed in various tissues including the skeletal muscle [75,76,77]. For example, three weeks of HFD (45% kcal) feeding in C57BL/6J mice downregulates oxidative phosphorylation gene expression as well as expression of Pgc-1α [75].…”

“…Specifically in the skeletal muscle, HFD-induced obesity is associated with the accumulation of FAO intermediates in the form of long and medium chain acylcarnitines in the skeletal muscle that occurs as a result of incomplete beta oxidation [76,82,119]. Accumulation of acylcarnitines as a consequence of incomplete mitochondrial beta oxidation of fatty acids is associated with development of insulin resistance in the skeletal muscle [140].…”

Quercetin supplementation does not enhance cerebellar mitochondrial biogenesis and oxidative status in exercised rats

“…As a matter of fact, a dose of 0.05 mg/d for 8 weeks improved the metabolic status of mice fed a high-fat diet through PGC-1α activation, although such effects did not become apparent, neither after 3 weeks of supplementation nor when quercetin was supplemented at a higher dose [37]. Furthermore, a dosage of 17 mg kg −1 d −1 improved mitochondrial content and function in mice fed both high-and low-fat diets for 9 weeks [42]. Thus, to reach a reliable conclusion regarding quercetin supplementation as an ergogenic agent, further studies must be performed, with a focus on matching length and dose with oxidant/antioxidant status and physiological adaptations.…”

Efecto del extracto etanólico de las hojas de Annona muricata L (guanabana) sobre Síndrome metabólico inducido en ratas

“…Diversos estudios evidenciaron que animales que recibieron quercetina, el alcaloide más importante encontrado en extractos de Anonna muricata, presentaron una disminución del peso corporal, disminución de la acumulación de grasa a nivel hepático e intestinal, así como también mejoró la hiperglicemia, hiperinsulinemia y dislipidemia, después que recibieron una dieta con alto contenido calórico más colesterol y sucrosa, los cuales desarrollaron obesidad y síndrome metabólico (13,15) . La quercetina actúa mejorando el estrés oxidativo y la expresión de PPARα en el hígado y los niveles de triglicéridos en el plasma, atenuando la acumulación de grasa a nivel visceral y hepático.…”