Developing and Implementing Racial Health Equity Plans in Four Large US Cities: A Qualitative Study.

CONTEXT: Local health departments (LHDs) and their partners are critical components of the fight for racial health equity, particularly given the variation in levels of, and pathways to, inequities at the local level. OBJECTIVE: To inform continued progress in this area, we qualitatively examined the development and implementation of equity-related plans and initiatives of LHDs within 4 large US cities: Baltimore, Boston, Chicago, and Philadelphia. DESIGN AND MEASURES: We conducted 15 semistructured interviews with 21 members of LHDs, academic institutions, health systems, and community-based organizations involved with health equity strategies or activities in their respective cities. Outcomes included perceptions of the effectiveness of the local health equity plan, participation in other equity-related initiatives, stakeholder engagement, and best practices. RESULTS: We contacted 49 individuals, of whom 2 declined and 21 accepted our interview invitation. Recruitment was stopped after we reached saturation. Thematic analysis identified 5 themes across interviews: (1) organizations were flexible in reallocating resources to address racial and health equity; (2) multidisciplinary teams are necessary for effective development and implementation of health equity plans; (3) community collaboration is required for meaningful and sustainable change; (4) there is a direct relationship between racism, structural inequities, and health outcomes; and (5) health departments have prioritized health equity plan development, but further work is required to address root causes. CONCLUSIONS: In the United States, health departments have begun to develop and implement strategic health plans focused on equity. However, the extent to which these plans result in actual initiatives (both internal and external) varied across cities. The current study increases our understanding of how different partners are working to implement structural changes, programs, and policies to reach equity-related goals in our largest urban areas, providing valuable insight for urban health advocates across the country.

The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr kinase activation.

Sestrins represent a family of stress-inducible proteins that prevent the progression of many age- and obesity-associated disorders. Endogenous Sestrins maintain insulin-dependent AKT Ser/Thr kinase (AKT) activation during high-fat diet-induced obesity, and overexpressed Sestrins activate AKT in various cell types, including liver and skeletal muscle cells. Although Sestrin-mediated AKT activation improves metabolic parameters, the mechanistic details underlying such improvement remain elusive. Here, we investigated how Sestrin2, the Sestrin homolog highly expressed in liver, induces strong AKT activation. We found that two known targets of Sestrin2, mTOR complex (mTORC) 1 and AMP-activated protein kinase, are not required for Sestrin2-induced AKT activation. Rather, phosphoinositol 3-kinase and mTORC2, kinases upstream of AKT, were essential for Sestrin2-induced AKT activation. Among these kinases, mTORC2 catalytic activity was strongly up-regulated upon Sestrin2 overexpression in an in vitro kinase assay, indicating that mTORC2 may represent the major link between Sestrin2 and AKT. As reported previously, Sestrin2 interacted with mTORC2; however, we found here that this interaction occurs indirectly through GATOR2, a pentameric protein complex that directly interacts with Sestrin2. Deleting or silencing WDR24 (WD repeat domain 24), the GATOR2 component essential for the Sestrin2-GATOR2 interaction, or WDR59, the GATOR2 component essential for the GATOR2-mTORC2 interaction, completely ablated Sestrin2-induced AKT activation. We also noted that Sestrin2 also directly binds to the pleckstrin homology domain of AKT and induces AKT translocation to the plasma membrane. These results uncover a signaling mechanism whereby Sestrin2 activates AKT through GATOR2 and mTORC2.