OSCILLATORY LIPOLYSIS IN PERIFUSED ADIPOCYTES

Boston Medical Center, Boston MA

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Abstract

It is known that abnormal fat metabolism plays an important in the pathogenesis of obesity-related type 2 diabetes. There is also a growing consensus that adipose tissues is a dynamic organ that plays an important role not only in the regulation of glucose homeostasis, but in the regulation of the whole body energy fuel regulation, feeding behavior, and body composition. It has been shown that free fatty acids (FFA) oscillate rapidly in plasma. These oscillations have an average pulse duration of 5 minutes and are not driven by the rapid and are not driven by the rapid plasma insulin oscillation. There is evidence to suggest that the oscillations are modulated by the sympathetic nervous system, however adrenergic-blockage of the adipocyte does not remove the FFA oscillation. Since insulin and the sympathetic nervous system do not drive the FFA oscillation it is hypothesized that the FFA oscillation is driven by an intrinsic pacemaker in the adipocyte similar to that of pancreatic beta cell. The overall objective of this proposal is to characterize the oscillation in perifused. Isolated adipocytes to determine the mechanism of the oscillation. And to gain insight into the role that the oscillation may play. The specific aims are 1) are there FFA oscillations present in perifused isolated adipocytes, what are their characteristics, and do they vary by fat depot? 2) what is the mechanism of oscillatory FFA release within the adipocyte? And 3) are the FFA oscillations modulated by either insulin or catecholamines?