Why the study?
Does i.p. administration of siRNA encapsulated by glucan shells to silence TNF-α or osteopontin improve glucose tolerance in obese mice?
Does i.p. administration of siRNA encapsulated by glucan shells to silence TNF-α or osteopontin improve glucose tolerance in obese mice?
Targeted gene silencing of inflammatory cytokines in epididymal adipose tissue macrophages improves systemic glucose tolerance in obese mice, demonstrating a direct link between adipose tissue macrophages and systemic metabolism.
Supports ATM inflammation as a driver of glucose intolerance in obese mice; leaves open translation of GeRP silencing to human metabolic disease.
Adipose tissue (AT) inflammation and infiltration by macrophages is associated with insulin resistance and type 2 diabetes in obese humans, offering a potential target for therapeutics. However, whether AT macrophages (ATMs) directly contribute to systemic glucose intolerance has not been determined. The reason is the lack of methods to ablate inflammatory genes expressed in macrophages specifically localized within AT depots, leaving macrophages in other tissues unaffected. Here we report that i.p. administration of siRNA encapsulated by glucan shells in obese mice selectively silences genes in epididymal ATMs, whereas macrophages within lung, spleen, kidney, heart, skeletal muscle, subcutaneous (SubQ) adipose, and liver are not targeted. Such administration of GeRPs to silence the inflammatory cytokines TNF-α or osteopontin in epididymal ATMs of obese mice caused significant improvement in glucose tolerance. These data are consistent with the hypothesis that cytokines produced by ATMs can exacerbate whole-body glucose intolerance.
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Aouadi et al. (2013) studied this question.
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