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ABSTRACT: Aims/hypothesis
High fat diet (HFD)-induced insulin resistance (IR) is partially characterized by reduced skeletal muscle mitochondrial function and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1?) expression. Our previous study showed that a high dose of the bioflavonoid quercetin exacerbated HFD-induced IR; yet, others have demonstrated that quercetin improves insulin sensitivity. The aim of this study was to investigate whether differing doses of quercetin act in a time-dependent manner to attenuate HFD-induced IR in association with improved skeletal muscle mitochondrial function and PGC1? expression.Methods
C57BL/6J mice were fed HFD for 3 or 8 wks, with or without a low (50 ug/day; HF+50Q) or high (600 ug/day, HF+600Q) dose of quercetin. Whole body and metabolic phenotypes and insulin sensitivity were assessed. Skeletal muscle metabolomic analysis of acylcarnitines and PGC1? mRNA expression via qRT-PCR were measured.Results
Quercetin at 50 ug/day for 8 wk attenuated HFD-induced increases in fat mass, body weight and IR and increased PGC1? expression, whereas 600 ug/day of quercetin exacerbated fat mass accumulation without altering body weight, IR or PGC1?. PGC1? expression correlated with acylcarnitine levels similarly in HF and HF+600Q; these correlations were not present in HF+50Q. At both time points, energy expenditure increased in HF+50Q and decreased in HF+600Q, independent of PGC1? and IR.Conclusions/interpretation
Chronic dietary quercetin supplementation at low but not higher dose ameliorates the development of diet-induced IR while increasing PGC1? expression in muscle, suggesting that skeletal muscle may be an important target for the insulin-sensitizing effects of a low dose of quercetin.
SUBMITTER: Henagan TM
PROVIDER: S-EPMC3931728 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Henagan Tara M TM Lenard Natalie R NR Gettys Thomas W TW Stewart Laura K LK
PloS one 20140221 2
<h4>Aims/hypothesis</h4>High fat diet (HFD)-induced insulin resistance (IR) is partially characterized by reduced skeletal muscle mitochondrial function and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1α) expression. Our previous study showed that a high dose of the bioflavonoid quercetin exacerbated HFD-induced IR; yet, others have demonstrated that quercetin improves insulin sensitivity. The aim of this study was to investigate whether differing doses of quercetin ...[more]