Obesity is associated with chronic low-grade
inflammation. Within adipose tissue of mice fed a high fat diet, resident and infiltrating macrophages assume a pro-inflammatory phenotype characterized by the production of
cytokines which in turn impact on the surrounding tissue. However,
inflammation is not restricted to adipose tissue and high fat-feeding is responsible for a significant increase in pro-inflammatory
cytokine expression in muscle. Although skeletal muscle is the major disposer of dietary
glucose and a major determinant of glycemia, the origin and consequence of muscle
inflammation in the development of
insulin resistance are poorly understood.We used a cell culture approach to investigate the vectorial crosstalk between muscle cells and macrophages upon exposure to physiological, low levels of saturated and
unsaturated fatty acids. Inflammatory pathway activation and
cytokine expression were analyzed in L6 muscle cells expressing myc-tagged GLUT4 (L6GLUT4myc) exposed to 0.2 mM
palmitate or
palmitoleate.
Conditioned media thereof, free of
fatty acids, were then tested for their ability to activate RAW264.7 macrophages.Palmitate -but not
palmitoleate- induced
IL-6, TNFα and CCL2 expression in muscle cells, through activation of the NF-κB pathway.
Palmitate (0.2 mM) alone did not induce
insulin resistance in muscle cells, yet
conditioned media from
palmitate-challenged muscle cells selectively activated macrophages towards a pro-inflammatory phenotype.These results demonstrate that low concentrations of
palmitate activate autonomous
inflammation in muscle cells to release factors that turn macrophages pro-inflammatory. We hypothesize that saturated fat-induced, low-grade muscle cell
inflammation may trigger resident skeletal muscle macrophage polarization, possibly contributing to
insulin resistance in vivo.