Journal
PLOS ONE
Volume 9, Issue 2, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0089365
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Funding
- National Center for Complementary and Alternative Medicine pilot grants [P50 AT002776]
- Botanicals Research Center at Pennington Biomedical Research Center in Baton Rouge, LA
- ADA [1-12-BS-58]
- NIH [RO1 DK-096311, P20-GM-103528]
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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 alpha) 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 alpha 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 alpha 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 alpha expression, whereas 600 ug/day of quercetin exacerbated fat mass accumulation without altering body weight, IR or PGC1 alpha. PGC1 alpha 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 alpha and IR. Conclusions/Interpretation: Chronic dietary quercetin supplementation at low but not higher dose ameliorates the development of diet-induced IR while increasing PGC1 alpha expression in muscle, suggesting that skeletal muscle may be an important target for the insulin-sensitizing effects of a low dose of quercetin.
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