Potential solutions for pediatric weight loss programs in the treatment of obesity in rural communities.

Pediatric obesity remains disproportionately more prevalent in rural communities; however, multidisciplinary, pediatric weight loss programs, which are often located in tertiary-care centers, may not be accessible to rural families. Limited models to specifically address pediatric obesity in rural communities exist. Therefore, innovative solutions are required for expanded treatment of pediatric obesity in rural communities. This article discusses potential solutions for multidisciplinary, tertiary-care pediatric weight loss programs to improve access and treatment of pediatric obesity in rural communities. A selected review of the literature suggests that strategies to overcome barriers to treatment in rural communities include telephone calls and telemedicine conferencing by obesity specialists from academic centers (obesity medicine specialists, endocrinologists, dietitians, and psychotherapists) as well as training local primary care providers in rural communities to screen, diagnose, and treat patients with obesity. Multidisciplinary, tertiary-care pediatric weight loss programs have a profound opportunity to impact the treatment of pediatric obesity in rural communities by training practicing rural primary care providers as well as strengthening their commitment to educate future generations of clinicians on the treatment of pediatric obesity through medical training including physician assistant, nurse practitioner, and pediatric and family medicine resident education and skill building. This article identifies potential mechanisms for expansive treatment of pediatric obesity in rural communities by multidisciplinary, tertiary-care weight loss programs and highlights areas of specific focus needed for future investigation.

A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids.

The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes. Herein, we describe proof-of-principle studies leading to the design, synthesis and enzymatic activity of several novel, ß-lactone-based, dual inhibitors of these two enzymes. Validation of dual enzyme targeting through activity-based proteome profiling with an alkyne probe modeled after the most potent inhibitor, and preliminary serum stability studies of selected derivatives are also described. These results provide proof of concept for dual targeting of the proteasome and fatty acid synthase-thioesterase (FAS-TE) enabling a new approach for the development of drug-candidates with potential to overcome resistance.