Circadian Cycle and Metabolic Dysfunction
Posted April 22, 2010
Ever since the first life forms developed, evolution has confronted the problem of timing: when should the organism eat, when should it reproduce, when should it rest? Across a span of nearly four billion years, our ancestors evolved to rise at dawn, sleep at dusk, feast in fall and fast in the winter.
That ancient schedule is still programmed into our genes, and we ignore it at our peril. Indeed, a growing body of evidence shows that the modern habits of waking to an alarm clock, sleeping after the "Tonight Show", and feasting all year round are largely responsible for some of the worst health problems of modern humans. The Academy's Diabetes and Obesity Discussion Group met on February 9, 2010 to discuss this interaction, in a meeting that featured presentations and a lively panel discussion by four leading researchers in the field.
Use the tabs above to find a meeting report and multimedia from this event.
Books and Web Site
Wirz-Justice A, Benedetti F, Terman M. 2009. Chronotherapeutics for Affective Disorders: a Clinician's Manual for Light and Wake Therapy. S. Karger AG, Switzerland.
Rodgers JT, Haas W, Gygi SG, Puigserver P. 2010. Cdc2-like Kinase 2 is an insulin regulated suppressor of hepatic gluconeogenesis. Cell Metab. 11: 23-34.
Cheng Z, Guo S, Copps K, et al. 2009. Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nat. Med. 15: 1307-1311.
Dominy JE, Lee Y, Gerhart-Hines Z, Puigserver P. 2009. Nutrient-dependent regulation of PGC-1alpha's acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5. Biochim. Biophys. Acta [Epub ahead of print.]
Garbarino-Pico E, Green CB. 2007. Posttranscriptional regulation of mammalian circadian clock output. Cold Spring Harb. Symp. Quant. Biol.72: 145-156.
Douris N, Green CB. 2008. NOC out the fat: a short review of the circadian deadenylase Nocturnin. Ann. Med. 40: 622-626.
Green CB, Takahashi JS, Bass J. 2008. The meter of metabolism. Cell 134: 728-742. Full Text
Davis C, Levitan RD. 2005. Seasonality and seasonal affective disorder (SAD): An evolutionary viewpoint tied to energy conservation and reproductive cycles. J. Affect. Disord. 87: 3-10.
Dunai A, Novak M, Chung SA, et al. 2007. Moderate exercise and bright light treatment in overweight and obese individuals. Obesity (Silver Spring) 15: 1749-1757.
Levitan RD, Masellis M, Lam RW, et al. 2006. A birth season/DRD4 gene interaction predicts weight gain and obesity in women with seasonal affective disorder: a seasonal thrifty phenotype hypothesis. Neuropsychopharmacology 31: 2498-2503.
Benedetti F, Barbini B, Fulgosi MC, et al. 2005. Combined total sleep deprivation and light therapy in the treatment of drug-resistant bipolar depression: acute response and long-term remission rates. J. Clin. Psychiatry 66: 1535-1540.
Joe Bass, MD, PhD
Joseph Bass is an associate professor in the Department of Medicine, Division of Molecular Medicine and Endocrinology, at the Northwestern University Feinberg School of Medicine, and in the Department of Neurobiology and Physiology. The major research focus of his group is on the molecular integration of circuits coordinating feeding, sleep, and wakefulness with systems controlling energy balance and nutrient utilization. This work stems from recent discoveries on the role of the circadian clock gene network in the integration of both brain and peripheral tissue energy sensing and metabolism. The Bass lab exploits approaches ranging from cell biology, to whole animal physiology, experimental genetics and behavioral analyses in order to elucidate the pathophysiology of diabetes, obesity, and metabolic syndrome in states of circadian and sleep disruption, and the reciprocal interplay between metabolic disease states and circadian disorders.
Carla Green, PhD
Carla Green is a professor of neuroscience at the University of Texas Southwestern Medical Center. She received her PhD from the Department of Biochemistry and Molecular Biology at the University of Kansas Medical Center where she worked on the structure and function of a human prostate-specific gene with Simon Kwok. Her postdoctoral research with Joseph Besharse in the Department of Anatomy and Cell Biology at the University of Kansas Medical Center marked the beginning of her interest in circadian biology. While in the Besharse lab she identified a number of circadian clock-controlled genes, including a novel rhythmic gene Nocturnin, in the Xenopus retina
After starting her own lab at the University of Virginia in 1997, she continued to use that model system to study molecular mechanisms of retinal clock function, developing tools to perturb clock function molecularly in transgenic Xenopus. She also continued her studies on the Nocturnin gene and demonstrated that this gene encodes a deadenylase—a polyA-specific ribonuclease that removes the polyA tails from mRNAs. More recently, her lab has begun to focus on mammalian model systems and, in addition to a continued focus on Nocturnin and its role in clock control of metabolism, also works on the role of the Cryptochrome proteins in the central circadian mechanism.
In September of 2009, she moved to the University of Texas Southwestern Medical Center to join the Department of Neuroscience. Carla Green is a fellow of the American Association for the Advancement of Science.
Robert Levitan, MD
Robert Levitan is an expert on atypical subtypes of mood disorders characterized by depressed mood and increased eating behavior, including atypical depression, seasonal affective disorder, and eating disorders such as binge eating disorder and bulimia nervosa. In many cases, these various disorders co-exist in the same individual, suggesting that one or more vulnerability factors are shared among them. Levitan integrates clinical research in adults with developmental research focused on the early origins of disease. This includes both genetic association studies and novel methodologies emerging from the rapidly evolving field of socio-biology, which focuses on the interplay of nature and nurture. A better understanding of the complexity inherent in these disorders will lead to new prevention strategies and treatment approaches.
Levitan is a senior clinical investigator in the mood disorders clinic at the Centre for Addiction and Mental Health, Toronto and is a full professor in the Department of Psychiatry at the University of Toronto. Levitan is also the immediate past-president of the Society for Light Treatment and Biological Rhythms (SLTBR).
Pere Puigserver, PhD
Pere Puigserver received his PhD in biochemistry from the University of Illes Balears, Spain, in 1992. He did postdoctoral research with Bruce Spiegelman at DFCI before joining the faculty as an assistant professor of cell biology at Johns Hopkins University School of Medicine in 2002. In 2006, Puigserver rejoined the faculty of Harvard Medical School and DFCI to continue his research on the genetic and biochemical mechanisms underlying the control of intermediary metabolism by nutrients and hormonal signals in mammals. In 2008 Puigserver was promoted to associate professor of cell biology at Harvard Medical School and Dana-Farber Cancer Institute.
Michael Terman, PhD
Michael Terman is professor of clinical psychology in Psychiatry at Columbia University, research scientist VI at the New York State Psychiatric Institute, director of the Center for Light Treatment and Biological Rhythms at New York-Presbyterian Hospital / Columbia University Medical Center (www.columbia-chronotherapy.org), and president of the Center for Environmental Therapeutics () an independent 501(c)(3) nonprofit consortium of mental health clinicians and chronobiologists. His animal research has focused on circadian rhythmicity in visual sensory and retinal function, circadian entrainment by feeding schedules, and the zeitgeber properties of naturalistic dawn-dusk transitions. His clinical research has led to the development of 10,000 lux light therapy, dawn simulation therapy, and negative air ionization therapy for depressive disorders. He is a co-author of the first treatment manual in the field, "Chronotherapeutics for Affective Disorders" (Karger, 2009).
Alan Dove is a science writer and reporter for Nature Medicine, Nature Biotechnology, and Bioscience Technology. He also teaches at the NYU School of Journalism, and blogs at http://dovdox.com.