High fat diet‐induced muscle insulin resistance: role of cytokines and local macrophages

Abstract

Obesity is characterized by adipose tissue expansion as well as macrophage infiltration of adipose tissue, resulting in chronic inflammation in adipose tissue, which in turn has a causative role in obesity‐induced insulin resistance. During state of chronic inflammation, levels of inflammatory markers, such as IL‐1b, TNF‐a, IL‐6 increase as a result of macrophage accumulation and activation, specifically a subset of inflammatory F4/80+CD11c+ macrophage/dendritic cells in adipose tissue. It is well recognized that increased production of free fatty acids and cytokine secretion from inflamed fat tissue induce insulin resistance in other insulin‐sensitive organs, such as skeletal muscle and liver. However, whether obesity also results in skeletal muscle inflammation and whether macrophage infiltration in muscle contributes to the development of insulin resistance has not been fully elucidated. We investigated inflammatory cytokine expression and mechanisms involved in the induction of insulin resistance and infiltrated local macrophages and other immune cells in skeletal muscle tissue in diet‐induced obese mice using qRT‐PCR. We found that F4/80+, Cd11b+ macrophages and Cd11c dendritic cells were most abundant immune cells infiltrated into skeletal muscle tissue and increased in response to high fat diet feeding, while mRNA expression of cell markers for CD4+, CD8+ T cells and CD19+ B cells were lower.