Pre-Clinical Optimization of Human Brown Adipocyte Cell Therapy

Presently available pharmacotherapy for diabetes and pre-diabetes can be effective initially, but the natural history of these conditions typically features deterioration of blood sugar control over time and the accumulation of disability. Importantly, the current treatment approaches do not halt the underlying disease. Approved drugs for overweight and obesity have only limited efficacy and most are associated with either significant side effects or safety risks. While bariatric surgical approaches can produce very effective weight loss, they are highly invasive and have significant risks of morbidity and mortality. Brown adipose tissue (BAT) is a major site of energy expenditure through thermogenesis, and has been shown to be a critical regulator of blood sugar and weight. Studies in animals as well as recent data in humans strongly suggest that modestly increasing BAT levels can improve glucose metabolism, cholesterol profiles, and weight. We recently demonstrated in proof-of-concept studies that cell therapy with brown adipocytes produces highly significant improvements in glucose control, weight, and body composition. The proposed work aims to optimize this approach for clinical application and pave the way for initiating studies of brown adipocyte cell therapy in patients.