Statins activate the NLRP3 inflammasome and impair insulin signalling via p38 and mTOR.

Statins activate the NLRP3 inflammasome and impair insulin signalling via p38 and mTOR. Am J Physiol Endocrinol Metab. 2020 May 18;: Authors: Henriksbo BD, Tamrakar AK, Phulka JS, Barra NG, Schertzer JD Abstract Statins lower cholesterol and risk of cardiovascular disease. Statins can increase blood glucose and risk of new onset diabetes. It is unclear why statins can have opposing effects on lipids versus glucose. Statins have cholesterol-independent pleiotropic effects that influence both insulin and glucose control. Statin lowering of isoprenoids required for protein prenylation promotes pancreatic beta cell dysfunction and adipose tissue insulin-resistance. Protein prenylation influences immune function and statin-mediated adipose tissue insulin resistance involves the NLRP3 inflammasome and IL-1b. However, the intracellular cues that statins engage to activate the NLRP3 inflammasome and those responsible for IL-1b-mediated insulin resistance in adipose tissue have not been identified. We hypothesized that stress kinases or components of the insulin signalling pathway mediated statin-induced insulin resistance. We tested the associations of p38, ERK, JNK, PTEN and mTOR in statin exposed adipose tissue from WT and IL-1b-/- mice. We found that statins increased phosphorylation of p38 in WT and IL-1b-/- mice. Statin activation of p38 upstream of IL-1b led to priming of this NLRP3 inflammasome effector in macrophages. We found that m...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research