Free fatty acids are able to promote inflammation in macrophages and other cells, a signaling mechanism that is key to understanding the relationships between obesity, lipid flux, inflammation and insulin resistance. One model posited that saturated fatty acids can directly activate TLR4 receptors, data that was supported by resistance to palmitate-induced JNK activation in Tlr4 knockouts.
Lancaster et al. and the Mark Febbraio lab present several studies arguing against that simple model, and instead provide very compelling data that supports the hypothesis that palmitate does not signal directly, but instead suggests that non-FFA TLR4 activation primes cells to respond to fatty acids through an alternate mechanism.They show that this TLR4-dependent priming effect on JNK is rapamycin sensitive, and is associated with changes in ER stress, and reduced induction of several bioactive lipids. Understanding the precise mechanisms and consequences of inflammation-induced reprogramming, and the extent to which this occurs in other cell types will be fascinating to follow.
Free fatty acids are able to promote inflammation in macrophages and other cells, a signaling mechanism that is key to understanding the relationships between obesity, lipid flux, inflammation and insulin resistance. One model posited that saturated fatty acids can directly activate TLR4 receptors, data that was supported by resistance to palmitate-induced JNK activation in Tlr4 knockouts.
Lancaster et al. and the Mark Febbraio lab present several studies arguing against that simple model, and instead provide very compelling data that supports the hypothesis that palmitate does not signal directly, but instead suggests that non-FFA TLR4 activation primes cells to respond to fatty acids through an alternate mechanism.They show that this TLR4-dependent priming effect on JNK is rapamycin sensitive, and is associated with changes in ER stress, and reduced induction of several bioactive lipids. Understanding the precise mechanisms and consequences of inflammation-induced reprogramming, and the extent to which this occurs in other cell types will be fascinating to follow.
These comments are cross-posted at Faculty of 1000 Prime.Written on , last modified on .