•Ganoderma lucidum polysaccharides (GLP) ameliorated low grade chronic inflammation.
•GLP ameliorated non-esterified fatty acid outflux and ectopic lipid accumulation.
•GLP improved systemic insulin sensitivity.
•GLP changed the composition of gut microbiota.
Ectopic lipid accumulation and low-grade chronic inflammation are critical pathogenesis of insulin resistance development. Ganoderma lucidum is a traditional Chinese herb for balancing energy homeostasis. In this research, we determined the effects of G. lucidum polysaccharides (GLP) on high-fat diet (HFD)-induced insulin resistant mice. We observed that GLP treatment decreased plasma insulin concentration and reversed HFD-induced systemic insulin resistance. Meanwhile, GLP ameliorated low-grade chronic inflammation, inducing lipolysis in adipose tissues. GLP decreased plasma triglyceride and non-esterified fatty acid outflux by suppressing mRNA expressions of hormone-sensitive lipase, fatty acid binding protein 4, tumor necrosis factor-α, and interleukin-6 in epididymal fat. Finally, GLP treatment suppressed ectopic lipid accumulation in peripheral tissues and hepatic insulin-regulated lipogenesis. GLP also regulated composition of gut microbiota implicated in type 2 diabetes mellitus development.
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