Cardiac myocyte KLF5 regulates body weight via alteration of cardiac FGF21.

Cardiac metabolism affects systemic energetic balance. Previously, we showed that Krüppel-like factor (KLF)-5 regulates cardiomyocyte PPARα and fatty acid oxidation-related gene expression in diabetes. We surprisingly found that cardiomyocyte-specific KLF5 knockout mice (αMHC-KLF5-/-) have accelerated diet-induced obesity, associated with increased white adipose tissue (WAT). Alterations in cardiac expression of the mediator complex subunit 13 (Med13) modulates obesity. αMHC-KLF5-/- mice had reduced cardiac Med13 expression likely because KLF5 upregulates Med13 expression in cardiomyocytes. We then investigated potential mechanisms that mediate cross-talk between cardiomyocytes and WAT. High fat diet-fed αMHC-KLF5-/- mice had increased levels of cardiac and plasma FGF21, while food intake, activity, plasma leptin, and natriuretic peptides expression were unchanged. Consistent with studies reporting that FGF21 signaling in WAT decreases sumoylation-driven PPARγ inactivation, αMHC-KLF5-/- mice had less SUMO-PPARγ in WAT. Increased diet-induced obesity found in αMHC-KLF5-/- mice was absent in αMHC-[KLF5-/-;FGF21-/-] double knockout mice, as well as in αMHC-FGF21-/- mice that we generated. Thus, cardiomyocyte-derived FGF21 is a component of pro-adipogenic crosstalk between heart and WAT.

Restricting mitochondrial GRK2 post-ischemia confers cardioprotection by reducing myocyte death and maintaining glucose oxidation.

Increased abundance of GRK2 [G protein-coupled receptor (GPCR) kinase 2] is associated with poor cardiac function in heart failure patients. In animal models, GRK2 contributes to the pathogenesis of heart failure after ischemia-reperfusion (IR) injury. In addition to its role in down-regulating activated GPCRs, GRK2 also localizes to mitochondria both basally and post-IR injury, where it regulates cellular metabolism. We previously showed that phosphorylation of GRK2 at Ser670 is essential for the translocation of GRK2 to the mitochondria of cardiomyocytes post-IR injury in vitro and that this localization promotes cell death. Here, we showed that mice with a S670A knock-in mutation in endogenous GRK2 showed reduced cardiomyocyte death and better cardiac function post-IR injury. Cultured GRK2-S670A knock-in cardiomyocytes subjected to IR in vitro showed enhanced glucose-mediated mitochondrial respiratory function that was partially due to maintenance of pyruvate dehydrogenase activity and improved glucose oxidation. Thus, we propose that mitochondrial GRK2 plays a detrimental role in cardiac glucose oxidation post-injury.

Orthodontic care for underserved patients: professional attitudes and behavior of orthodontic residents and orthodontists.

OBJECTIVES: To explore whether orthodontic residents and orthodontists differ in their attitudes and behavior concerning the treatment of underserved patients and to investigate how background factors such as the providers' gender, ethnicity/race, and age affect these attitudes and behavior. MATERIALS AND METHODS: Survey data were collected from 135 residents in US and Canadian graduate orthodontic programs and from 568 active members of the American Association of Orthodontists. Attitudes toward various aspects of treating underserved patients were rated on a five-point scale, with 1 indicating the most negative attitude and 5 indicating the most positive. RESULTS: Orthodontic residents had more positive attitudes about treating poor patients (3.02 vs 1.99; P < .001), pro bono cases (3.87 vs. 3.45; P < .001), and patients with craniofacial anomalies (3.64 vs 3.01; P < .001) or mental retardation (3.13 vs 2.72; P < .001) than orthodontists. However, compared to orthodontists, lower percentages of residents intended to treat pro bono cases (73.5% vs 83%; P = .009) and patients with craniofacial anomalies (63.6% vs 82.9%; P < .001) or mental retardation (55% vs 81.5%; P < .001). The providers' gender did not have an effect on these attitudes and related behavior, while ethnicity/race and age of the providers were relevant. CONCLUSIONS: Residents had more positive attitudes concerning the treatment of underserved patients than orthodontists. However, their behavioral intentions did not indicate an increased willingness to provide care for these patients.

Orthodontists' and orthodontic residents' education in treating underserved patients: effects on professional attitudes and behavior.

The U.S. surgeon general's report on oral health in 2000 stressed the importance of providing dental care for underserved patient groups. Given that orthodontic treatment is less likely to be covered by dental plans than other procedures and is often considered an elective treatment, it is not surprising that access to orthodontic care is an especially severe problem for underserved patient groups. The purpose of this study was to explore the degree to which orthodontic residents and orthodontists perceived that their graduate orthodontic education had prepared them well to treat underserved patients and whether this education affected their professional attitudes and behavior concerning providing care for members of historically underserved patient groups. Survey data were collected from 135 residents in U.S. and Canadian graduate orthodontic programs and from 568 active members of the American Association of Orthodontists (AAO). While the majority of residents and orthodontists felt well prepared to treat patients from different ethnic/racial backgrounds (quality of clinical education: residents: 86.4 percent; orthodontists: 82.3 percent), considerably fewer respondents felt well prepared to treat patients on Medicaid (64.7 percent and 34.4 percent), pro bono cases (45.4 percent and 33.4 percent), patients with special needs (52.8 percent and 35 percent), patients with craniofacial anomalies (65.3 percent and 52.6 percent), and patients with developmental delays (45.5 percent and 30.5 percent). Perceptions of the quality of education correlated significantly with the professional attitudes and the actual/projected behavior concerning providing care for patients from these underserved patient groups. Given the lack of access to orthodontic care for patients from underserved patient groups, initiatives are needed to change this situation. These findings showed a clear relationship between how future orthodontists are educated about providing care for patients from underserved populations and their professional attitudes and behavioral intentions to provide care for individuals who historically have encountered access to care barriers. Dental education has to accept the responsibility to prepare future dental care providers to be able to treat patients from underserved groups.