David Sparling, MD, PhD awarded the Pediatric Endocrine Society Research Fellowship
David Sparling, MD, PhD, a Fellow in the Division of Pediatric Endocrinology, Diabetes, and Metabolism at Columbia University Medical Center received the Pediatric Endocrine Society Research Fellowship Award for $50,000 to support his last year of fellowship.
Dr. Sparling also won the Society for Pediatric Research's Fellow Basic Research Award for his work on The Role of Notch in Adipose Tissue, which is to be presented at the Pediatric Academic Society.
The Role of Notch in Adipose Tissue
The Notch signaling cascade, classically associated with cell-fate decisions, has been found to aid in metabolic regulation in the liver. Notch can also regulate muscle fiber-type specificity and adipocyte differentiation with the insulin-responsive transcription factor FoxO1. While Notch activity appears to regulate adipocyte differentiation in vitro, no study has yet addressed the role of Notch in fully differentiated adipose depots, or its role in regulation of adipocyte-type specification. In children and adults higher brown adipose tissue (BAT) mass has been inversely correlated to BMI and therefore increased BAT activity might protect against diet-induced obesity. Furthermore, expansion of BAT activity may be achieved through “browning” of established white adipose tissue (WAT). Recent data has proven that browning occurs from de novo differentiation of adipocyte precursors resident in subcutaneous, and to a much lesser extent, visceral WAT depots. Interestingly, Notch target expression is decreased in visceral adipose but significantly increased in BAT following cold exposure, with a correlative increase in the classic brown adipose marker Uncoupling protein 1 (Ucp1). We have developed mice with adipose-specific knockout of Nicastrin (A-Ncst), a component of the γ-secretase complex required for Notch activity. We are currently examining multiple cohorts of A-Ncst mice under various metabolic conditions, and determining expression levels of Notch targets and brown- and white-adipose markers using quantitative RT-PCR, to determine the role of Notch in regulation of developed adipose tissue and its possible effects on whole body metabolism.