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Adipose tissue insulin resistance (Adipo-IR) results in excessive release of free fatty acids from adipose tissue, which plays a key role in the development of"lipotoxicity".Therefore, amelioration of Adipo-IR may benefit the treatment of other metabolic abnormalities.Here we found that treatment with the alcoholic extract of ginger (50 mg/kg/day, by oral gavage) for five weeks attenuated liquid fructose-induced hyperinsulinemia and increase in the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats.More importantly, ginger reversed the increases in the Adipo-IR index and plasma non-esterified fatty acid concentrations during the oral glucose tolerance test assessment.Adipose gene/protein expression profiles revealed that ginger treatment suppressed CD68 and F4/80, two important macrophage accumulation markers.Consistently, the macrophage-associated cytokines tissue necrosis factor-alpha and interleukin-6 were also downregulated.In contrast, insulin receptor substrate (IRS)-1, but not IRS-2, was upregulated.Moreover, monocyte chemotactic protein (MCP)-1 and its receptor chemokine (C-C motif) receptor-2 were also suppressed.Thus these results suggest that amelioration of fructose-induced Adipo-IR by ginger treatment in rats is associated with suppression of adipose macrophage-related pro-inflammatory cytokines.