Blocking AMPK ß1 myristoylation enhances AMPK activity and protects mice from high-fat diet-induced obesity and hepatic steatosis.

AMP-activated protein kinase (AMPK) is a master regulator of cellular energy homeostasis and a therapeutic target for metabolic diseases. Co/post-translational N-myristoylation of glycine-2 (Gly2) of the AMPK ß subunit has been suggested to regulate the distribution of the kinase between the cytosol and membranes through a "myristoyl switch" mechanism. However, the relevance of AMPK myristoylation for metabolic signaling in cells and in vivo is unclear. Here, we generated knockin mice with a Gly2-to-alanine point mutation of AMPKß1 (ß1-G2A). We demonstrate that non-myristoylated AMPKß1 has reduced stability but is associated with increased kinase activity and phosphorylation of the Thr172 activation site in the AMPK α subunit. Using proximity ligation assays, we show that loss of ß1 myristoylation impedes colocalization of the phosphatase PPM1A/B with AMPK in cells. Mice carrying the ß1-G2A mutation have improved metabolic health with reduced adiposity, hepatic lipid accumulation, and insulin resistance under conditions of high-fat diet-induced obesity.

Role of Gender and Race in Patient-Reported Outcomes and Satisfaction.

The role of gender, race, and socioeconomic status in outcomes and satisfaction are reflected in patient-reported outcomes using measurement tools representing outcome domains. These domains include pain relief, physical and emotional functioning, adverse events, participant disposition, and patient satisfaction. Measurement tools exist for each of the outcomes in both acute and chronic pain. Patients with lower economic status have greater difficulty accessing care, are involved less in shared decision-making process, and are less satisfied with their care. Blacks, Hispanics, and Asians also have increased difficulty in accessing good quality care. Women have inferior outcomes after medical and surgical interventions.