AMPK as a Therapeutic Target for Treating Metabolic Diseases. (August 2017) - Day, Emily A.
Abstract : The AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways and may have therapeutic importance for treating obesity, insulin resistance, type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Given the ubiquitous expression of AMPK, it has been a challenge to evaluate which tissue types may be most beneficially poised for mediating the positive metabolic effects of AMPK-centered treatments. In this review we evaluate the metabolic phenotypes of transgenic mouse models in which AMPK expression and function have been manipulated, and the impact this has on controlling lipid metabolism, glucose homeostasis, and inflammation. This information may be useful for guiding the development of AMPK-targeted therapeutics to treat chronic metabolic diseases. Trends: Macrophage AMPK promotes an anti-inflammatory phenotype and reverse cholesterol transport, and protects against obesity-induced insulin resistance. Hepatic AMPK is important for preventing liver lipid accumulation and insulin resistance, but does not directly inhibit hepatic glucose production. AMPK is required for maintaining mitochondrial function in brown adipose tissue, and protects against hypothermia, obesity-induced NAFLD, and insulin resistance.