I am a neuroendocrinologist by training, having received my Bachelor’s degree in biochemistry and molecular biology from the University of California, Santa Barbara and Master’s and Doctorate degrees from Louisiana State University (LSU) in physiology under the mentorship of Dr. Albert H. Meier. It was at LSU that my interest in the biological clock system and its role in the regulation of metabolic physiology was sparked by the revolutionary discoveries and elucidations made by Dr. Meier’s lab concerning biological clock mechanisms regulating physiology. He and his group in the early 1960s were the very first to demonstrate the existence in any organism of circadian rhythms of physiological responses to neuroendocrine factors. More importantly, in subsequent years this group unlocked the biological code to the expression of seasonal changes in physiology among all the major classes of vertebrates from fish to mammals that had remained an intriguing mystery to man since antiquity. In very short, it was concluded that seasonality changes in physiology were the result of phase changes in circadian neuroendocrine events at the biological clock system in the brain that were not dependent upon changes in photoperiod. Seasonal changes in metabolism have been preserved over 400 million years of evolution and impart a strategy for survival of a predictable ensuing seasonal low/no food (glucose) availability by becoming obese/insulin resistant at the correct time of year and by means independent of food consumption or energy expenditure.
I therefore began investigating at LSU the possibility that modern human pathology of the metabolic syndrome (and several other progressive pathologies) was not a result of any “genetic defect” but of an environmentally induced (e.g., diet, stress, sleep-wake architecture) alteration of circadian neuroendocrine information presented to the clock system that then responded to direct the body to the obese/insulin resistant state as a survival response to such information. After completing my PhD at LSU, I continued there as a postdoctoral fellow under Dr. Meier and then as a faculty member for some time before joining the faculty at Harvard Medical School and Massachusetts General Hospital to continue investigating the connection between neuroendocrine regulation of the biological clock system and its subsequent regulation of physiology to determine if an environmentally imposed derangement of clock regulation such as modern western life style may influence metabolism and metabolic disease. It was found that alterations in circadian neuroendocrine information received by the clock system in the brain could “program” the clock to direct (via its widespread connections of the autonomic nervous system and endocrine system) the body towards (or away) from the metabolic syndrome depending upon the circadian input signals to the clock and independent of food consumption.
During this investigational journey I founded and directed two biotech companies to use this information to construct a treatment paradigm for metabolic diseases, including Type 2 Diabetes Mellitus (T2DM), that resulted in the FDA approval of the only circadian-based neuroendocrine therapy for T2DM: morning administration of Cycloset®, a dopamine D2 receptor agonist. The following four newsletters will cover the salient discoveries made by our laboratories along the way within this line of biological investigation and highlight the nature of powerful biological clock mechanisms that regulate metabolism, including metabolic behavior. We will discuss how environmental influences can be interpreted by the clock system as “stress” or signals for “impending stress” (e.g., westernized diet as an evolutionary signal for future food scarcity) that program the clock to direct the body towards its survival mode, the obese, insulin resistant state, but under prolonged (not seasonal) circumstances lead to eventual pathology and how these neuroendocrine events may be “re-programmed” to revert the system from pathology to physiology.